"Too Fat" Part Three!...
Això és la continuació del tema "Too Fat" Part Two!....
En/na "Too Fat" Part Four!... ha continuat aquest tema.
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1margd
High Prevotella: Bacterioides ratio correlates to weight loss on high fiber diet:
Will You Lose Weight? Take A Look At Your Poop
Bruce Y. Lee
...Researchers from the University of Copenhagen, the Technical University of Denmark, the Steno Diabetes Center Copenhagen, and Gelesis Inc. measured and calculated the ratio of two bacteria, Prevotella and Bacteroides, in the poop from 62 people who were overweight. Then, the researchers randomly assigned the study participants to receive for 26 weeks either the ad libitum New Nordic Diet (NND), which high in fiber and wholegrains, or an Average Danish Diet (ADD).
The results? Among those with a high Prevotella to Bacteroides ratio, study participants on the high fiber (or NND) diet lost on average 3.15 kg (or 6.94 pounds) more body fat than those on the average Danish diet. By contrast, the two diets did not result in any significant difference among those with low Prevotella to Bacteroides ratios. In other words, different bacteria, different responses to the diet.
...Oh, poo, you may say, what if you are stuck with a "bad" microbiome? Well, evidence suggests that different things that you put in your mouth can affect your microbiome such as medications (especially antibiotics) and the food that you eat. Your surroundings such as pollution may also influence your microbiome composition. Although more research is needed to determine how exactly your diet and other factors may affect the bacteria in your intestines and how interventions such as probiotics may help, minimizing antibiotic use is one thing you may want to do immediately...
https://www.forbes.com/sites/brucelee/2017/09/16/will-you-lose-weight-take-a-loo...
_______________________________________________________
M F Hjorth et al. 2017. Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention. International Journal of Obesity accepted article preview 8 September 2017; doi: 10.1038/ijo.2017.220 . http://www.nature.com/ijo/journal/vaop/naam/abs/ijo2017220a.html?foxtrotcallback...
Abstract. Based on the abundance of specific bacterial genera, the human gut microbiota can be divided into two relatively stable groups that might play a role in personalized nutrition. We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets. A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/wholegrain or an Average Danish Diet (ADD) for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models. Among individuals with high P/B the NND resulted in a 3.15 kg (95%CI 1.55;4.76, P...) larger body fat loss compared to ADD whereas no differences was observed among individuals with low P/B (0.88 kg 95% CI −0.61;2.37, P...). Consequently, a 2.27 kg (95%CI 0.09;4.45, P...) difference in responsiveness to the diets were found between the two groups. In summary, subjects with high P/B-ratio appeared more susceptible to lose body fat on diets high in fiber and wholegrain than subjects with a low P/B-ratio.
________________________________________________________
New Nordic Diet:
...Rich in plant foods (often foraged), the diet includes lots of root vegetables, cabbage (and other crucifers), dark greens, apples and pears, berries (such as ligonberries and bilberries) and whole grains (such as rye and oats). Fish (such as salmon and herring) is also prominent, along with some wild game (such as elk, inherently low in fat) and small amounts of dairy. Other wild foods include moss, mushrooms, nettles, garlic and even ants. Fresh herbs include dill, chives and fennel. For dessert, how about some barley pudding?
In many ways, the New Nordic Diet is very similar to a Mediterranean diet but relies on rapeseed (canola) oil instead of olive oil and differs in its types of produce (few tomatoes here), simply as a reflection of what the region’s climate, soil and water naturally—and best—produce...
http://www.berkeleywellness.com/healthy-eating/diet-weight-loss/article/new-nord...
________________________________________________________
A Paleo afficionado ponders relationships among Prevotella, meat & other foods, whole grain consumption, TMAO, atherosclerosis...
http://humanfoodproject.com/from-meat-to-microbes-to-main-street-is-it-time-to-t...
Will You Lose Weight? Take A Look At Your Poop
Bruce Y. Lee
...Researchers from the University of Copenhagen, the Technical University of Denmark, the Steno Diabetes Center Copenhagen, and Gelesis Inc. measured and calculated the ratio of two bacteria, Prevotella and Bacteroides, in the poop from 62 people who were overweight. Then, the researchers randomly assigned the study participants to receive for 26 weeks either the ad libitum New Nordic Diet (NND), which high in fiber and wholegrains, or an Average Danish Diet (ADD).
The results? Among those with a high Prevotella to Bacteroides ratio, study participants on the high fiber (or NND) diet lost on average 3.15 kg (or 6.94 pounds) more body fat than those on the average Danish diet. By contrast, the two diets did not result in any significant difference among those with low Prevotella to Bacteroides ratios. In other words, different bacteria, different responses to the diet.
...Oh, poo, you may say, what if you are stuck with a "bad" microbiome? Well, evidence suggests that different things that you put in your mouth can affect your microbiome such as medications (especially antibiotics) and the food that you eat. Your surroundings such as pollution may also influence your microbiome composition. Although more research is needed to determine how exactly your diet and other factors may affect the bacteria in your intestines and how interventions such as probiotics may help, minimizing antibiotic use is one thing you may want to do immediately...
https://www.forbes.com/sites/brucelee/2017/09/16/will-you-lose-weight-take-a-loo...
_______________________________________________________
M F Hjorth et al. 2017. Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention. International Journal of Obesity accepted article preview 8 September 2017; doi: 10.1038/ijo.2017.220 . http://www.nature.com/ijo/journal/vaop/naam/abs/ijo2017220a.html?foxtrotcallback...
Abstract. Based on the abundance of specific bacterial genera, the human gut microbiota can be divided into two relatively stable groups that might play a role in personalized nutrition. We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets. A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/wholegrain or an Average Danish Diet (ADD) for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models. Among individuals with high P/B the NND resulted in a 3.15 kg (95%CI 1.55;4.76, P...) larger body fat loss compared to ADD whereas no differences was observed among individuals with low P/B (0.88 kg 95% CI −0.61;2.37, P...). Consequently, a 2.27 kg (95%CI 0.09;4.45, P...) difference in responsiveness to the diets were found between the two groups. In summary, subjects with high P/B-ratio appeared more susceptible to lose body fat on diets high in fiber and wholegrain than subjects with a low P/B-ratio.
________________________________________________________
New Nordic Diet:
...Rich in plant foods (often foraged), the diet includes lots of root vegetables, cabbage (and other crucifers), dark greens, apples and pears, berries (such as ligonberries and bilberries) and whole grains (such as rye and oats). Fish (such as salmon and herring) is also prominent, along with some wild game (such as elk, inherently low in fat) and small amounts of dairy. Other wild foods include moss, mushrooms, nettles, garlic and even ants. Fresh herbs include dill, chives and fennel. For dessert, how about some barley pudding?
In many ways, the New Nordic Diet is very similar to a Mediterranean diet but relies on rapeseed (canola) oil instead of olive oil and differs in its types of produce (few tomatoes here), simply as a reflection of what the region’s climate, soil and water naturally—and best—produce...
http://www.berkeleywellness.com/healthy-eating/diet-weight-loss/article/new-nord...
________________________________________________________
A Paleo afficionado ponders relationships among Prevotella, meat & other foods, whole grain consumption, TMAO, atherosclerosis...
http://humanfoodproject.com/from-meat-to-microbes-to-main-street-is-it-time-to-t...
2margd
Greta Lazutkaite et al. 2017, Amino acid sensing in hypothalamic tanycytes via umami taste receptors. Molecular Metabolism.
DOI: http://dx.doi.org/10.1016/j.molmet.2017.08.015 | http://www.molmetab.com/article/S2212-8778(17)30537-9/abstract
...4.2. Similarities between tanycytes and taste receptor cells
...The detection of circulating nutrients by tanycytes, thus, is remarkably similar to that of taste sensing in the tongue both in the types of receptors involved and the consequent downstream signaling via channel-mediated release of ATP. Thus, tanycytes should be thought of as general nutrient sensors in the hypothalamus.
4.3. Amino acid detection in the brain
...Our discovery that tanycytes also sense amino acids in the CSF (cerebrospinal fluid) via at least two receptors is an important advance that suggests: 1) that tanycytes are anorexigenic; and 2) that they might act with the neural networks in the hypothalamus to regulate food intake...
5. Conclusions
Hypothalamic tanycytes are directly sensitive to a range of essential and non-essential amino acids, which are important signals of satiety...Our data warrant investigation as to whether tanycytes may be physiological mediators of satiety signals and act to reduce food intake.
______________________________________
Chicken, plums and lentils make you fuller quicker, study claims
The foods that just got healthier
Olivia Petter | 28 September 2017
...Apricots, plums, almonds, lentils and pork shoulder, chicken, sirloin steak, avocadoes and almonds all boast high concentrations of amino acids and therefore make people feel fuller quicker than other foods.
...Dr Nicholas Dale, Professor of Neuroscience at the university (of Warwick)...“Finding that tanycytes, located at the centre of the brain region that controls body weight, directly sense amino acids has very significant implications for coming up with new ways to help people to control their body weight within healthy bounds.”
Dale and his team came across the effect after they directly added a high dosage of amino acids into the brain.
The tanycytes responded just thirty seconds later, sending signals to the brain that manages appetite and would stimulate feelings of fullness.
The findings could be key in developing appetite-suppressants...
http://www.independent.co.uk/life-style/food-and-drink/chicken-plums-lentils-fil...
DOI: http://dx.doi.org/10.1016/j.molmet.2017.08.015 | http://www.molmetab.com/article/S2212-8778(17)30537-9/abstract
...4.2. Similarities between tanycytes and taste receptor cells
...The detection of circulating nutrients by tanycytes, thus, is remarkably similar to that of taste sensing in the tongue both in the types of receptors involved and the consequent downstream signaling via channel-mediated release of ATP. Thus, tanycytes should be thought of as general nutrient sensors in the hypothalamus.
4.3. Amino acid detection in the brain
...Our discovery that tanycytes also sense amino acids in the CSF (cerebrospinal fluid) via at least two receptors is an important advance that suggests: 1) that tanycytes are anorexigenic; and 2) that they might act with the neural networks in the hypothalamus to regulate food intake...
5. Conclusions
Hypothalamic tanycytes are directly sensitive to a range of essential and non-essential amino acids, which are important signals of satiety...Our data warrant investigation as to whether tanycytes may be physiological mediators of satiety signals and act to reduce food intake.
______________________________________
Chicken, plums and lentils make you fuller quicker, study claims
The foods that just got healthier
Olivia Petter | 28 September 2017
...Apricots, plums, almonds, lentils and pork shoulder, chicken, sirloin steak, avocadoes and almonds all boast high concentrations of amino acids and therefore make people feel fuller quicker than other foods.
...Dr Nicholas Dale, Professor of Neuroscience at the university (of Warwick)...“Finding that tanycytes, located at the centre of the brain region that controls body weight, directly sense amino acids has very significant implications for coming up with new ways to help people to control their body weight within healthy bounds.”
Dale and his team came across the effect after they directly added a high dosage of amino acids into the brain.
The tanycytes responded just thirty seconds later, sending signals to the brain that manages appetite and would stimulate feelings of fullness.
The findings could be key in developing appetite-suppressants...
http://www.independent.co.uk/life-style/food-and-drink/chicken-plums-lentils-fil...
3margd
Both black and green tea reduce weight in mice fed high fat diet, but some difference in mechanisms:
Susanne M. Henning et al. 2017. Decaffeinated green and black tea polyphenols decrease weight gain and alter microbiome populations and function in diet-induced obese mice. Eur J Nutr (2017). https://doi.org/10.1007/s00394-017-1542-8 . https://link.springer.com/article/10.1007/s00394-017-1542-8
__________________________________________________________________
Tea Aids Weight Loss through Microbiome Alteration
October 4, 2017
...investigators at UCLA have demonstrated that tea, and in particular black tea, may promote weight loss and other health benefits by changing bacteria within the gut. Findings from the new study...show that in mice black tea alters energy metabolism in the liver by changing gut metabolites.
"It was known that green tea polyphenols (GTPs) are more effective and offer more health benefits than black tea polyphenols (BTPs) since green tea chemicals are absorbed into the blood and tissue," explained lead study investigator Susanne Henning, Ph.D., an adjunct professor at the UCLA Center for Human Nutrition, which is part of the David Geffen School of Medicine at UCLA. "Our new findings suggest that black tea, through a specific mechanism through the gut microbiome, may also contribute to good health and weight loss in humans."
Interestingly, the study found that both black and green tea changed the ratio of intestinal bacteria in the animals: The percentage of bacteria associated with obesity decreased, while bacteria associated with lean body mass increased.
"The results suggest that both green and black teas are prebiotics, substances that induce the growth of good microorganisms that contribute to a person's well-being," Dr. Henning noted.
Previous studies have indicated that chemicals in green tea called polyphenols are absorbed and alter the energy metabolism in the liver. The new findings show that BTPs, which are too large to be absorbed in the small intestine, stimulate the growth of gut bacterium and the formation of short-chain fatty acids, a type of bacterial metabolites that have been shown to alter the energy metabolism in the liver.
In the current study, four groups of mice received different diets—two of which were supplemented with green tea or black tea extracts:
· Low-fat, high-sugar;
· High-fat, high-sugar;
· High-fat, high-sugar and green tea extract;
· High-fat, high-sugar and black tea extract.
Amazingly, the research team found that after four weeks the weights of the mice that were given green or black tea extracts dropped to the same levels as those of the mice that received the low-fat diet throughout the study. Moreover, the investigators collected samples from the mice's large intestines (to measure bacteria content) and liver tissues (to measure fat deposits). In the mice that consumed either type of tea extract, there was less of the type of bacteria associated with obesity and more of the bacteria associated with lean body mass.
However, only the mice that consumed black tea extract had an increase in a type of bacteria called Pseudobutyrivibrio, which could help explain the difference between how black tea and green tea change energy metabolism.
...The researchers noted that these new findings suggest the health benefits of both green tea and black tea go beyond their antioxidant benefits and that both teas have a strong impact on the gut microbiome.
"For black tea lovers, there may be a new reason to keep drinking it," concluded senior study investigator Zhaoping Li, M.D., director of the UCLA Center for Human Nutrition and chief of the UCLA Division of Clinical Nutrition.
http://www.genengnews.com/gen-news-highlights/tea-aids-weight-loss-through-micro...
Susanne M. Henning et al. 2017. Decaffeinated green and black tea polyphenols decrease weight gain and alter microbiome populations and function in diet-induced obese mice. Eur J Nutr (2017). https://doi.org/10.1007/s00394-017-1542-8 . https://link.springer.com/article/10.1007/s00394-017-1542-8
__________________________________________________________________
Tea Aids Weight Loss through Microbiome Alteration
October 4, 2017
...investigators at UCLA have demonstrated that tea, and in particular black tea, may promote weight loss and other health benefits by changing bacteria within the gut. Findings from the new study...show that in mice black tea alters energy metabolism in the liver by changing gut metabolites.
"It was known that green tea polyphenols (GTPs) are more effective and offer more health benefits than black tea polyphenols (BTPs) since green tea chemicals are absorbed into the blood and tissue," explained lead study investigator Susanne Henning, Ph.D., an adjunct professor at the UCLA Center for Human Nutrition, which is part of the David Geffen School of Medicine at UCLA. "Our new findings suggest that black tea, through a specific mechanism through the gut microbiome, may also contribute to good health and weight loss in humans."
Interestingly, the study found that both black and green tea changed the ratio of intestinal bacteria in the animals: The percentage of bacteria associated with obesity decreased, while bacteria associated with lean body mass increased.
"The results suggest that both green and black teas are prebiotics, substances that induce the growth of good microorganisms that contribute to a person's well-being," Dr. Henning noted.
Previous studies have indicated that chemicals in green tea called polyphenols are absorbed and alter the energy metabolism in the liver. The new findings show that BTPs, which are too large to be absorbed in the small intestine, stimulate the growth of gut bacterium and the formation of short-chain fatty acids, a type of bacterial metabolites that have been shown to alter the energy metabolism in the liver.
In the current study, four groups of mice received different diets—two of which were supplemented with green tea or black tea extracts:
· Low-fat, high-sugar;
· High-fat, high-sugar;
· High-fat, high-sugar and green tea extract;
· High-fat, high-sugar and black tea extract.
Amazingly, the research team found that after four weeks the weights of the mice that were given green or black tea extracts dropped to the same levels as those of the mice that received the low-fat diet throughout the study. Moreover, the investigators collected samples from the mice's large intestines (to measure bacteria content) and liver tissues (to measure fat deposits). In the mice that consumed either type of tea extract, there was less of the type of bacteria associated with obesity and more of the bacteria associated with lean body mass.
However, only the mice that consumed black tea extract had an increase in a type of bacteria called Pseudobutyrivibrio, which could help explain the difference between how black tea and green tea change energy metabolism.
...The researchers noted that these new findings suggest the health benefits of both green tea and black tea go beyond their antioxidant benefits and that both teas have a strong impact on the gut microbiome.
"For black tea lovers, there may be a new reason to keep drinking it," concluded senior study investigator Zhaoping Li, M.D., director of the UCLA Center for Human Nutrition and chief of the UCLA Division of Clinical Nutrition.
http://www.genengnews.com/gen-news-highlights/tea-aids-weight-loss-through-micro...
42wonderY
>3 margd: And I read recently that high fructose corn syrup increases the fat storage in the liver.
My daughter has switched from sodas to tea (black tea mostly, and all day long) and her weight is going down while her energy levels increase. It has made a remarkable difference in her life.
Nice to know some of the background biochemistry.
My daughter has switched from sodas to tea (black tea mostly, and all day long) and her weight is going down while her energy levels increase. It has made a remarkable difference in her life.
Nice to know some of the background biochemistry.
5margd
(My brainstem made me eat that IC! :-)
Scientists engineer proteins that caused obese animals to lose weight and lower cholesterol
Melissa Healy | Oct 19, 2017
...Scientists from the biotechnology company Amgen Inc. report they have identified and improved upon a naturally occurring protein that brought about significant changes in obese mice and monkeys, including weight loss and rapid improvements on measures of metabolic and heart health.
...In mice who got a bioengineered version of the GDF15 protein, the researchers observed even more remarkable changes. These obese mice turned their noses up at extra-rich condensed milk — a treat that normally prompts mice to gorge themselves. Given the choice, the treated mice tended to opt for standard mouse chow instead, or at least lowered their intake of the fattening condensed milk.
Nearly 4 in 10 U.S. adults are now obese, CDC says
After 35 days, obese mice treated with the bioengineered GDF15 proteins lost roughly 20% of their body weight, while mice getting a placebo gained about 6% over their starting weight, according to the study. When mice were offered the rich condensed milk, triglyceride levels remained at baseline or rose by about 20% in those who got the engineered proteins, while levels more than doubled in the untreated mice. Insulin levels and total cholesterol readings were also significantly better in treated animals than in their untreated counterparts.
The results suggest that the GDF15 engineered by researchers had the power to turn off the kind of reward-driven eating (think doughnuts, milkshakes or bacon cheeseburgers) that drives many of us to become obese, or to regain lost weight.
...In the brains of the lab animals that received the treatment, the study authors detected activation in a population of brain-stem cells that transmits complex signals between the brain and gut.
In obese people, those signals — which urge us to eat when we’re hungry and to stop once we’ve eaten — become faulty, causing us to overeat and gain weight. Bariatric surgery appears to correct those signals.
So the suggestion that GDF15 might do the same is an exciting indication that a piece of bariatric surgery’s magic might be bottled up in a pill...
http://www.latimes.com/science/sciencenow/la-sci-sn-weight-loss-protein-20171019...
____________________________________________________________
Yumei Xiong et al. 2017. Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys. See all authors and affiliations
Science Translational Medicine 18 Oct 2017: Vol. 9, Issue 412, eaan8732 . DOI: 10.1126/scitranslmed.aan8732 . http://stm.sciencemag.org/content/9/412/eaan8732
A bigger molecule to help slim down
Obesity is becoming increasingly common worldwide, and the available interventions do not fully address this problem. Surgery is currently the most effective intervention, especially for severe obesity, but it carries more risks than noninvasive treatments and produces permanent side effects. Xiong et al. searched for metabolically regulated proteins and identified the growth differentiation factor 15 (GDF15) pathway as a potential target for intervention. The loss of this protein in mice is associated with weight gain and worsened metabolic parameters. Conversely, the authors showed that treating with GDF15 improved metabolic health in mice, rats, and monkeys. They also designed a modified version of GDF15 (GDF15-Fc fusion) that has a longer half-life and would thus be a better candidate for clinical testing.
Abstract
In search of metabolically regulated secreted proteins, we conducted a microarray study comparing gene expression in major metabolic tissues of fed and fasted ob/ob mice and C57BL/6 mice. The array used in this study included probes for ~4000 genes annotated as potential secreted proteins. Circulating macrophage inhibitory cytokine 1 (MIC-1)/growth differentiation factor 15 (GDF15) concentrations were increased in obese mice, rats, and humans in comparison to age-matched lean controls. Adeno-associated virus–mediated overexpression of GDF15 and recombinant GDF15 treatments reduced food intake and body weight and improved metabolic profiles in various metabolic disease models in mice, rats, and obese cynomolgus monkeys. Analysis of the GDF15 crystal structure suggested that the protein is not suitable for conventional Fc fusion at the carboxyl terminus of the protein. Thus, we used a structure-guided approach to design and successfully generate several Fc fusion molecules with extended half-life and potent efficacy. Furthermore, we discovered that GDF15 delayed gastric emptying, changed food preference, and activated area postrema neurons, confirming a role for GDF15 in the gut-brain axis responsible for the regulation of body energy intake. Our work provides evidence that GDF15 Fc fusion proteins could be potential therapeutic agents for the treatment of obesity and related comorbidities.
Scientists engineer proteins that caused obese animals to lose weight and lower cholesterol
Melissa Healy | Oct 19, 2017
...Scientists from the biotechnology company Amgen Inc. report they have identified and improved upon a naturally occurring protein that brought about significant changes in obese mice and monkeys, including weight loss and rapid improvements on measures of metabolic and heart health.
...In mice who got a bioengineered version of the GDF15 protein, the researchers observed even more remarkable changes. These obese mice turned their noses up at extra-rich condensed milk — a treat that normally prompts mice to gorge themselves. Given the choice, the treated mice tended to opt for standard mouse chow instead, or at least lowered their intake of the fattening condensed milk.
Nearly 4 in 10 U.S. adults are now obese, CDC says
After 35 days, obese mice treated with the bioengineered GDF15 proteins lost roughly 20% of their body weight, while mice getting a placebo gained about 6% over their starting weight, according to the study. When mice were offered the rich condensed milk, triglyceride levels remained at baseline or rose by about 20% in those who got the engineered proteins, while levels more than doubled in the untreated mice. Insulin levels and total cholesterol readings were also significantly better in treated animals than in their untreated counterparts.
The results suggest that the GDF15 engineered by researchers had the power to turn off the kind of reward-driven eating (think doughnuts, milkshakes or bacon cheeseburgers) that drives many of us to become obese, or to regain lost weight.
...In the brains of the lab animals that received the treatment, the study authors detected activation in a population of brain-stem cells that transmits complex signals between the brain and gut.
In obese people, those signals — which urge us to eat when we’re hungry and to stop once we’ve eaten — become faulty, causing us to overeat and gain weight. Bariatric surgery appears to correct those signals.
So the suggestion that GDF15 might do the same is an exciting indication that a piece of bariatric surgery’s magic might be bottled up in a pill...
http://www.latimes.com/science/sciencenow/la-sci-sn-weight-loss-protein-20171019...
____________________________________________________________
Yumei Xiong et al. 2017. Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys. See all authors and affiliations
Science Translational Medicine 18 Oct 2017: Vol. 9, Issue 412, eaan8732 . DOI: 10.1126/scitranslmed.aan8732 . http://stm.sciencemag.org/content/9/412/eaan8732
A bigger molecule to help slim down
Obesity is becoming increasingly common worldwide, and the available interventions do not fully address this problem. Surgery is currently the most effective intervention, especially for severe obesity, but it carries more risks than noninvasive treatments and produces permanent side effects. Xiong et al. searched for metabolically regulated proteins and identified the growth differentiation factor 15 (GDF15) pathway as a potential target for intervention. The loss of this protein in mice is associated with weight gain and worsened metabolic parameters. Conversely, the authors showed that treating with GDF15 improved metabolic health in mice, rats, and monkeys. They also designed a modified version of GDF15 (GDF15-Fc fusion) that has a longer half-life and would thus be a better candidate for clinical testing.
Abstract
In search of metabolically regulated secreted proteins, we conducted a microarray study comparing gene expression in major metabolic tissues of fed and fasted ob/ob mice and C57BL/6 mice. The array used in this study included probes for ~4000 genes annotated as potential secreted proteins. Circulating macrophage inhibitory cytokine 1 (MIC-1)/growth differentiation factor 15 (GDF15) concentrations were increased in obese mice, rats, and humans in comparison to age-matched lean controls. Adeno-associated virus–mediated overexpression of GDF15 and recombinant GDF15 treatments reduced food intake and body weight and improved metabolic profiles in various metabolic disease models in mice, rats, and obese cynomolgus monkeys. Analysis of the GDF15 crystal structure suggested that the protein is not suitable for conventional Fc fusion at the carboxyl terminus of the protein. Thus, we used a structure-guided approach to design and successfully generate several Fc fusion molecules with extended half-life and potent efficacy. Furthermore, we discovered that GDF15 delayed gastric emptying, changed food preference, and activated area postrema neurons, confirming a role for GDF15 in the gut-brain axis responsible for the regulation of body energy intake. Our work provides evidence that GDF15 Fc fusion proteins could be potential therapeutic agents for the treatment of obesity and related comorbidities.
6margd
In mice, suspected association between gut fungi and obesity:
Gut fungi might be linked to obesity...
Yeast and bacteria can team up to cause trouble
Tina Hesman Saey | October 16, 2017
...High-fat diets may alter relationships between bacteria and fungi in mice’s intestines, contributing to obesity, researchers report October 11 in mSphere.
Cheryl Gale of the University of Minnesota in Minneapolis...fed mice either standard mouse chow or high-fat chow. As expected, mice on the high-fat diet gained weight, and the mix of bacteria in their guts shifted. Firmicutes bacteria associated with obesity increased, while Bacteroidetes bacteria decreased in abundance.
Fungi changed too. Mice fed high-fat chow had less Saccharomyces cerevisiae yeast and more Candida albicans in their guts than did mice that ate standard chow. S. cerevisiae is a yeast used in making wine, beer and bread and has been associated with good health. C. albicans is an organism that causes many yeast infections.
Gale’s team also discovered that relationships between bacteria and fungi changed when mice’s diets were changed. Her team can’t yet show a direct connection between the composition of gut fungi and obesity, but suspects that shifting interactions between bacteria and fungi might lead the host to gain weight...
_____________________________________________________
T. Heisel et al. High-fat diet changes fungal microbiomes and interkingdom relationships in the murine gut. mSphere. Vol. 2, October 11, 2017, p. e00351. doi: 10.1128/mSphere.00351-17 . http://msphere.asm.org/content/2/5/e00351-17
ABSTRACT
Dietary fat intake and shifts in gut bacterial community composition are associated with the development of obesity. To date, characterization of microbiota in lean versus obese subjects has been dominated by studies of gut bacteria. Fungi, recently shown to affect gut inflammation, have received little study for their role in obesity. We sought to determine the effects of high-fat diet on fungal and bacterial community structures in a mouse model using the internal transcribed spacer region 2 (ITS2) of fungal ribosomal DNA (rDNA) and the 16S rRNA genes of bacteria. Mice fed a high-fat diet had significantly different abundances of 19 bacterial and 6 fungal taxa than did mice fed standard chow, with high-fat diet causing similar magnitudes of change in overall fungal and bacterial microbiome structures. We observed strong and complex diet-specific coabundance relationships between intra- and interkingdom microbial pairs and dramatic reductions in the number of coabundance correlations in mice fed a high-fat diet compared to those fed standard chow. Furthermore, predicted microbiome functional modules related to metabolism were significantly less abundant in high-fat-diet-fed than in standard-chow-fed mice. These results suggest a role for fungi and interkingdom interactions in the association between gut microbiomes and obesity.
Gut fungi might be linked to obesity...
Yeast and bacteria can team up to cause trouble
Tina Hesman Saey | October 16, 2017
...High-fat diets may alter relationships between bacteria and fungi in mice’s intestines, contributing to obesity, researchers report October 11 in mSphere.
Cheryl Gale of the University of Minnesota in Minneapolis...fed mice either standard mouse chow or high-fat chow. As expected, mice on the high-fat diet gained weight, and the mix of bacteria in their guts shifted. Firmicutes bacteria associated with obesity increased, while Bacteroidetes bacteria decreased in abundance.
Fungi changed too. Mice fed high-fat chow had less Saccharomyces cerevisiae yeast and more Candida albicans in their guts than did mice that ate standard chow. S. cerevisiae is a yeast used in making wine, beer and bread and has been associated with good health. C. albicans is an organism that causes many yeast infections.
Gale’s team also discovered that relationships between bacteria and fungi changed when mice’s diets were changed. Her team can’t yet show a direct connection between the composition of gut fungi and obesity, but suspects that shifting interactions between bacteria and fungi might lead the host to gain weight...
_____________________________________________________
T. Heisel et al. High-fat diet changes fungal microbiomes and interkingdom relationships in the murine gut. mSphere. Vol. 2, October 11, 2017, p. e00351. doi: 10.1128/mSphere.00351-17 . http://msphere.asm.org/content/2/5/e00351-17
ABSTRACT
Dietary fat intake and shifts in gut bacterial community composition are associated with the development of obesity. To date, characterization of microbiota in lean versus obese subjects has been dominated by studies of gut bacteria. Fungi, recently shown to affect gut inflammation, have received little study for their role in obesity. We sought to determine the effects of high-fat diet on fungal and bacterial community structures in a mouse model using the internal transcribed spacer region 2 (ITS2) of fungal ribosomal DNA (rDNA) and the 16S rRNA genes of bacteria. Mice fed a high-fat diet had significantly different abundances of 19 bacterial and 6 fungal taxa than did mice fed standard chow, with high-fat diet causing similar magnitudes of change in overall fungal and bacterial microbiome structures. We observed strong and complex diet-specific coabundance relationships between intra- and interkingdom microbial pairs and dramatic reductions in the number of coabundance correlations in mice fed a high-fat diet compared to those fed standard chow. Furthermore, predicted microbiome functional modules related to metabolism were significantly less abundant in high-fat-diet-fed than in standard-chow-fed mice. These results suggest a role for fungi and interkingdom interactions in the association between gut microbiomes and obesity.
7margd
Osteocalcin produced in bone, activated by enzyme furin, has role in fat and sugar metabloism.
(Vitamin K also has function, I think, but what I'm not sure--paper lost me in Introduction...)
The weight loss secret to metabolising fat and sugar is in your bones
Paloma Sharma | Nov 2, 2017
...According to new study from Canada’s Montreal Clinical Research Institute (IRCM), your bones may hold the key to help you lose weight, keep off the fat and even prevent Type 2 diabetes – all due to a hormone called osteocalcin. Produced by the bones themselves, osteocalcin affects your appetite as well as your body’s ability to metabolise sugar and fat. The director of the Integrative and Molecular Physiology Research Unit at the IRCM, Dr Mathieu Ferron, was quoted by Bioscience Technology explaining how the discovery of this hormone and its functions could aid in making humankind a fitter species, “Osteocalcin helps, among other things, to produce insulin, which lowers the level of glucose in our blood. It could also protect us from obesity by increasing our energy expenditure. ”
Produced by single nucleus cells called osteoblasts, which are responsible for bone building, osteocalcin alone cannot help regulate sugar levels within the body. When osteocalcin is first produced through osteoblasts during the bone formation process, it is inactive. Researchers found that it needs to be acted upon by furin, a cellular endoproteinase, for it to transform into active osteocalcin – which is then released into the body’s blood stream, where it begins its work...
https://www.gqindia.com/content/weight-loss-metabolism-bones/
___________________________________________________________________________
Omar Al Rifai et al. 2017. Proprotein convertase furin regulates osteocalcin and bone endocrine function. J Clin Invest. 2017;127(11):4104-4117. doi:10.1172/JCI93437. https://www.jci.org/articles/view/93437/pdf
Abstract. Osteocalcin (OCN) is an osteoblast-derived hormone that increases energy expenditure, insulin sensitivity, insulin secretion,
and glucose tolerance. The cDNA sequence of OCN predicts that, like many other peptide hormones, OCN is first synthesized
as a prohormone (pro-OCN). The importance of pro-OCN maturation in regulating OCN and the identity of the endopeptidase
responsible for pro-OCN cleavage in osteoblasts are still unknown. Here, we show that the proprotein convertase furin is
responsible for pro-OCN maturation in vitro and in vivo. Using pharmacological and genetic experiments, we also determined
that furin-mediated pro-OCN cleavage occurred independently of its γ-carboxylation, a posttranslational modification that
is known to hamper OCN endocrine action. However, because pro-OCN is not efficiently decarboxylated and activated during
bone resorption, inactivation of furin in osteoblasts in mice resulted in decreased circulating levels of undercarboxylated OCN,
impaired glucose tolerance, and reduced energy expenditure. Furthermore, we show that Furin deletion in osteoblasts reduced
appetite, a function not modulated by OCN, thus suggesting that osteoblasts may secrete additional hormones that regulate
different aspects of energy metabolism. Accordingly, the metabolic defects of the mice lacking furin in osteoblasts became more
apparent under pair-feeding conditions. These findings identify furin as an important regulator of bone endocrine function.
Introduction...γ-Carboxylation of OCN (osteocalcin) occurs in the ER (Endoplasmic Reticulum??) and is mediated by γ-glutamyl carboxylase (GGCX), which requires reduced vitamin K as an essential cofactor (10). ... Here, we identified furin, using cell-based and genetic arguments, as the endopeptidase responsible for pro-OCN (osteocalcin) processing in osteoblasts. We also showed in cell culture and in vivo that γ-carboxylation and processing of OCN are 2 independent processes in osteoblasts. The study of mice lacking furin specifically in osteoblasts revealed that proteolysis of pro-OCN is critical for the activation of this hormone. We also found that furin may modulate energy metabolism through OCN-independent pathway(s) affecting appetite...
...10. Stafford DW. The vitamin K cycle. J Thromb Haemost. 2005;3(8):1873–1878....
(Vitamin K also has function, I think, but what I'm not sure--paper lost me in Introduction...)
The weight loss secret to metabolising fat and sugar is in your bones
Paloma Sharma | Nov 2, 2017
...According to new study from Canada’s Montreal Clinical Research Institute (IRCM), your bones may hold the key to help you lose weight, keep off the fat and even prevent Type 2 diabetes – all due to a hormone called osteocalcin. Produced by the bones themselves, osteocalcin affects your appetite as well as your body’s ability to metabolise sugar and fat. The director of the Integrative and Molecular Physiology Research Unit at the IRCM, Dr Mathieu Ferron, was quoted by Bioscience Technology explaining how the discovery of this hormone and its functions could aid in making humankind a fitter species, “Osteocalcin helps, among other things, to produce insulin, which lowers the level of glucose in our blood. It could also protect us from obesity by increasing our energy expenditure. ”
Produced by single nucleus cells called osteoblasts, which are responsible for bone building, osteocalcin alone cannot help regulate sugar levels within the body. When osteocalcin is first produced through osteoblasts during the bone formation process, it is inactive. Researchers found that it needs to be acted upon by furin, a cellular endoproteinase, for it to transform into active osteocalcin – which is then released into the body’s blood stream, where it begins its work...
https://www.gqindia.com/content/weight-loss-metabolism-bones/
___________________________________________________________________________
Omar Al Rifai et al. 2017. Proprotein convertase furin regulates osteocalcin and bone endocrine function. J Clin Invest. 2017;127(11):4104-4117. doi:10.1172/JCI93437. https://www.jci.org/articles/view/93437/pdf
Abstract. Osteocalcin (OCN) is an osteoblast-derived hormone that increases energy expenditure, insulin sensitivity, insulin secretion,
and glucose tolerance. The cDNA sequence of OCN predicts that, like many other peptide hormones, OCN is first synthesized
as a prohormone (pro-OCN). The importance of pro-OCN maturation in regulating OCN and the identity of the endopeptidase
responsible for pro-OCN cleavage in osteoblasts are still unknown. Here, we show that the proprotein convertase furin is
responsible for pro-OCN maturation in vitro and in vivo. Using pharmacological and genetic experiments, we also determined
that furin-mediated pro-OCN cleavage occurred independently of its γ-carboxylation, a posttranslational modification that
is known to hamper OCN endocrine action. However, because pro-OCN is not efficiently decarboxylated and activated during
bone resorption, inactivation of furin in osteoblasts in mice resulted in decreased circulating levels of undercarboxylated OCN,
impaired glucose tolerance, and reduced energy expenditure. Furthermore, we show that Furin deletion in osteoblasts reduced
appetite, a function not modulated by OCN, thus suggesting that osteoblasts may secrete additional hormones that regulate
different aspects of energy metabolism. Accordingly, the metabolic defects of the mice lacking furin in osteoblasts became more
apparent under pair-feeding conditions. These findings identify furin as an important regulator of bone endocrine function.
Introduction...γ-Carboxylation of OCN (osteocalcin) occurs in the ER (Endoplasmic Reticulum??) and is mediated by γ-glutamyl carboxylase (GGCX), which requires reduced vitamin K as an essential cofactor (10). ... Here, we identified furin, using cell-based and genetic arguments, as the endopeptidase responsible for pro-OCN (osteocalcin) processing in osteoblasts. We also showed in cell culture and in vivo that γ-carboxylation and processing of OCN are 2 independent processes in osteoblasts. The study of mice lacking furin specifically in osteoblasts revealed that proteolysis of pro-OCN is critical for the activation of this hormone. We also found that furin may modulate energy metabolism through OCN-independent pathway(s) affecting appetite...
...10. Stafford DW. The vitamin K cycle. J Thromb Haemost. 2005;3(8):1873–1878....
8margd
Cinnamon's essential oil that gives cinnamon its flavor, (cinnamaldehyde), "improves metabolic health by acting directly on fat cells, or adipocytes, inducing them to start burning energy through a process called thermogenesis."
Juan Jiang et al. 2017. Cinnamaldehyde induces fat cell-autonomous thermogenesis and metabolic reprogramming. Metabolism. December 2017Volume 77, Pages 58–64 . DOI: http://dx.doi.org/10.1016/j.metabol.2017.08.006 . http://www.metabolismjournal.com/article/S0026-0495(17)30212-3/fulltext
Conclusions. CA activates thermogenic and metabolic responses in mouse and human primary subcutaneous adipocytes in a cell-autonomous manner, giving a mechanistic explanation for the anti-obesity effects of CA observed previously and further supporting its potential metabolic benefits on humans. Given the wide usage of cinnamon in the food industry, the notion that this popular food additive, instead of a drug, may activate thermogenesis, could ultimately lead to therapeutic strategies against obesity that are much better adhered to by participants.
____________________________________________________
Cinnamon turns up the heat on fat cells
Emily Kagey | Nov 21, 2017
http://ns.umich.edu/new/releases/25273-cinnamon-turns-up-the-heat-on-fat-cells
Juan Jiang et al. 2017. Cinnamaldehyde induces fat cell-autonomous thermogenesis and metabolic reprogramming. Metabolism. December 2017Volume 77, Pages 58–64 . DOI: http://dx.doi.org/10.1016/j.metabol.2017.08.006 . http://www.metabolismjournal.com/article/S0026-0495(17)30212-3/fulltext
Conclusions. CA activates thermogenic and metabolic responses in mouse and human primary subcutaneous adipocytes in a cell-autonomous manner, giving a mechanistic explanation for the anti-obesity effects of CA observed previously and further supporting its potential metabolic benefits on humans. Given the wide usage of cinnamon in the food industry, the notion that this popular food additive, instead of a drug, may activate thermogenesis, could ultimately lead to therapeutic strategies against obesity that are much better adhered to by participants.
____________________________________________________
Cinnamon turns up the heat on fat cells
Emily Kagey | Nov 21, 2017
http://ns.umich.edu/new/releases/25273-cinnamon-turns-up-the-heat-on-fat-cells
9mamzel
>8 margd: I'm glad to hear this. I put plain cinnamon on my toast every morning (had to cut out sugar). Don't see much in the way of results yet or is this one of those things where you have to ingest huge quantities for the effect to work? (I would read the article but too many words with too many syllables makes my brain rebel. I have no clue what a subcutaneous adipocyte is. A fat cell, maybe?)
10margd
I know what you mean about the jargon!
(Wikipedia on adipose tissue: In humans, adipose tissue is located beneath the skin (subcutaneous fat), around internal organs (visceral fat), in bone marrow (yellow bone marrow), intermuscular (Muscular system) and in the breast tissue...adipocytes...comprise the highest percentage of cells within adipose tissue)
I remember looking for the actionable amount of cinnamon and not finding anything usable--can't access the paper now to look again... :-( One thing I was concerned about is that the info would resurrect recent teen practice of taking cinnamon by the spoonful--I seem to recall one kid died of it (aspiration).
For myself, I use such info as reason to include a food in my diet. Sometimes I keep a checklist of such foods on the fridge, such as MD Michael Greger's Daily Dozen. I'm no vegetarian but the list bends me toward better choices, I hope! He even has a free app! https://nutritionfacts.org/video/dr-gregers-daily-dozen-checklist/
(Wikipedia on adipose tissue: In humans, adipose tissue is located beneath the skin (subcutaneous fat), around internal organs (visceral fat), in bone marrow (yellow bone marrow), intermuscular (Muscular system) and in the breast tissue...adipocytes...comprise the highest percentage of cells within adipose tissue)
I remember looking for the actionable amount of cinnamon and not finding anything usable--can't access the paper now to look again... :-( One thing I was concerned about is that the info would resurrect recent teen practice of taking cinnamon by the spoonful--I seem to recall one kid died of it (aspiration).
For myself, I use such info as reason to include a food in my diet. Sometimes I keep a checklist of such foods on the fridge, such as MD Michael Greger's Daily Dozen. I'm no vegetarian but the list bends me toward better choices, I hope! He even has a free app! https://nutritionfacts.org/video/dr-gregers-daily-dozen-checklist/
11margd
Evidence found for a body-weight sensor in the long bones of the lower extremities that regulates fat. This New Year--resolve to walk, stand, weight-bearing leg exercises, not ignore Fitbit reminders? ;-)
Scientists Discover an Entirely New Biological System That Regulates Body Fat
Independent of diet and exercise.
DAVID NIELD | 29 DEC 2017
New research has identified a mechanism in the body that appears to act as a kind of internal bathroom scale, registering body weight and telling the brain to reduce or increase food intake as necessary.
..."The weight of the body is registered in the lower extremities. If the body weight tends to increase, a signal is sent to the brain to decrease food intake and keep the body weight constant."
...scientists fitted extra weights to already obese rodents and observed what happened.
When the extra weights were added to the mice, body fat decreased and blood glucose levels improved. In fact, the animals lost the same amount of weight as had been added.
...The precise workings of these internal scales – which have been dubbed the gravitostat – aren't yet clear, but based on follow-up tests the scientists think some of the sensing might be done by the bones lower down in the body.
What appears to be happening is that cells in the mice's bones - known as osteocytes - are somehow detecting the amount of weight and strain on bones, and then feed that message back to the brain....
https://www.sciencealert.com/study-discovers-internal-biological-scales-monitori...
_____________________________________________________-
John-Olov Jansson et al. 2017. Body weight homeostat that regulates fat mass independently of leptin in rats and mice. PNAS doi: 10.1073/pnas.1715687114 . http://www.pnas.org/content/early/2017/12/19/1715687114.full
Significance
The only known homeostatic regulator of fat mass is the leptin system. We hypothesized that there is a second homeostat regulating body weight with an impact on fat mass. In this study we have added and removed weight loads from experimental animals and measured the effects on the biological body weight. The results demonstrate that there is a body weight homeostat that regulates fat mass independently of leptin. As the body weight-reducing effect of increased loading was dependent on osteocytes, we propose that there is a sensor for body weight in the long bones of the lower extremities acting as “body scales.” This is part of a body weight homeostat, “gravitostat,” that keeps body weight and body fat mass constant.
Abstract
Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat (“gravitostat”) that regulates fat mass.
Scientists Discover an Entirely New Biological System That Regulates Body Fat
Independent of diet and exercise.
DAVID NIELD | 29 DEC 2017
New research has identified a mechanism in the body that appears to act as a kind of internal bathroom scale, registering body weight and telling the brain to reduce or increase food intake as necessary.
..."The weight of the body is registered in the lower extremities. If the body weight tends to increase, a signal is sent to the brain to decrease food intake and keep the body weight constant."
...scientists fitted extra weights to already obese rodents and observed what happened.
When the extra weights were added to the mice, body fat decreased and blood glucose levels improved. In fact, the animals lost the same amount of weight as had been added.
...The precise workings of these internal scales – which have been dubbed the gravitostat – aren't yet clear, but based on follow-up tests the scientists think some of the sensing might be done by the bones lower down in the body.
What appears to be happening is that cells in the mice's bones - known as osteocytes - are somehow detecting the amount of weight and strain on bones, and then feed that message back to the brain....
https://www.sciencealert.com/study-discovers-internal-biological-scales-monitori...
_____________________________________________________-
John-Olov Jansson et al. 2017. Body weight homeostat that regulates fat mass independently of leptin in rats and mice. PNAS doi: 10.1073/pnas.1715687114 . http://www.pnas.org/content/early/2017/12/19/1715687114.full
Significance
The only known homeostatic regulator of fat mass is the leptin system. We hypothesized that there is a second homeostat regulating body weight with an impact on fat mass. In this study we have added and removed weight loads from experimental animals and measured the effects on the biological body weight. The results demonstrate that there is a body weight homeostat that regulates fat mass independently of leptin. As the body weight-reducing effect of increased loading was dependent on osteocytes, we propose that there is a sensor for body weight in the long bones of the lower extremities acting as “body scales.” This is part of a body weight homeostat, “gravitostat,” that keeps body weight and body fat mass constant.
Abstract
Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat (“gravitostat”) that regulates fat mass.
12margd
Soluble fiber supplement reduced BMI, wt (~5lbs), fat, fasting glucose, fasting insulin (Am J Clin Nutr)
The inulin in study is widely available in pharmacies as a generic brand powder. (Made from chicory root.) Some gut conditions aggravated by soluble fiber, so do your homework. Increase gradually in diet, so you don't overstrip your microbiome and cause GIT distress. (I mix another soluble fiber in my coffee every morning (gum Arabic, Heather's).)
Variety of fibers best: fruits & veg, whole grains (like oatmeal), beans, etc. Plus the soluble fiber supplement? http://healthyeating.sfgate.com/sources-soluble-fiber-natural-foods-2125.html Also--probiotics like kefir
NYT article that follows Thomson et al. has great explanation of how fiber feeds microbiome that effects these effects and more:
Sharon V Thomson et al. 2017. Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. First published November 1, 2017, doi: 10.3945/ajcn.117.163246. http://ajcn.nutrition.org/content/early/2017/11/01/ajcn.117.163246.abstract
Abstract
Background: There is strong epidemiologic evidence that dietary fiber intake is protective against overweight and obesity; however, results of intervention studies have been mixed. Soluble fiber beneficially affects metabolism, and fiber supplementation may be a feasible approach to improve body composition and glycemia in adults with overweight and obesity.
Objective: We evaluated randomized controlled trials (RCTs) of isolated soluble fiber supplementation in overweight and obese adults on outcomes related to weight management (body mass index (BMI; in kg/m2), body weight, percentage of body fat, and waist circumference)and glucose and insulin metabolism (homeostasis model assessment of insulin resistance and fasting insulin) through a systematic review and meta-analysis.
Design: We searched PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Cochrane Library databases. Eligible studies were RCTs that compared isolated soluble fiber with placebo treatments without energy-restriction protocols...
Results: Findings from 12 RCTs (n = 609 participants) from 2 to 17 wk of duration are summarized in this review. Soluble fiber supplementation reduced BMI by 0.84...body weight by 2.52 kg...body fat by 0.41%...fasting glucose by 0.17 mmol/L...and fasting insulin by 15.88 pmol/L... compared with the effects of placebo treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes.
Conclusions: Isolated soluble fiber supplementation improves anthropometric and metabolic outcomes in overweight and obese adults, thereby indicating that supplementation may improve fiber intake and health in these individuals. However, the interpretation of these findings warrants caution because of the considerable between-study heterogeneity...
_______________________________________________________________________
Fiber Is Good for You. Now Scientists May Know Why.
Carl Zimmer | JAN. 1, 2018
A diet of fiber-rich foods, such as fruits and vegetables, reduces the risk of developing diabetes, heart disease and arthritis. Indeed, the evidence for fiber’s benefits extends beyond any particular ailment: Eating more fiber seems to lower people’s mortality rate, whatever the cause.
...But while the benefits are clear, it’s not so clear why fiber is so great.
,,,The ability of these bacteria to survive on fiber we can’t digest ourselves has led many experts to wonder if the microbes are somehow involved in the benefits of the fruits-and-vegetables diet. Two detailed studies published recently in the journal Cell Host and Microbe provide compelling evidence that the answer is yes.
In one experiment, Andrew T. Gewirtz of Georgia State University and his colleagues put mice on a low-fiber, high-fat diet. By examining fragments of bacterial DNA in the animals’ feces, the scientists were able to estimate the size of the gut bacterial population in each mouse.
On a low-fiber diet, they found, the population crashed, shrinking tenfold.
Dr. Bäckhed and his colleagues carried out a similar experiment, surveying the microbiome in mice as they were switched from fiber-rich food to a low-fiber diet. “It’s basically what you’d get at McDonald’s,” said Dr. Bäckhed said. “A lot of lard, a lot of sugar, and twenty percent protein.”
The scientists focused on the diversity of species that make up the mouse’s gut microbiome. Shifting the animals to a low-fiber diet had a dramatic effect, they found: Many common species became rare, and rare species became common.
Along with changes to the microbiome, both teams also observed rapid changes to the mice themselves. Their intestines got smaller, and its mucus layer thinner. As a result, bacteria wound up much closer to the intestinal wall, and that encroachment triggered an immune reaction.
After a few days on the low-fiber diet, mouse intestines developed chronic inflammation. After a few weeks, Dr. Gewirtz’s team observed that the mice began to change in other ways, putting on fat, for example, and developing higher blood sugar levels.
Dr. Bäckhed and his colleagues also fed another group of rodents the high-fat menu, along with a modest dose of a type of fiber called inulin. The mucus layer in their guts was healthier than in mice that didn’t get fiber, the scientists found, and intestinal bacteria were kept at a safer distance from their intestinal wall.
Dr. Gewirtz and his colleagues gave inulin to their mice as well, but at a much higher dose. The improvements were even more dramatic: Despite a high-fat diet, the mice had healthy populations of bacteria in their guts, their intestines were closer to normal, and they put on less weight.
Dr. Bäckhed and his colleagues ran one more interesting experiment: They spiked water given to mice on a high-fat diet with a species of fiber-feeding bacteria. The addition changed the mice for the better: Even on a high-fat diet, they produced more mucus in their guts, creating a healthy barrier to keep bacteria from the intestinal walls.
One way that fiber benefits health is by giving us, indirectly, another source of food, Dr. Gewirtz said. Once bacteria are done harvesting the energy in dietary fiber, they cast off the fragments as waste. That waste — in the form of short-chain fatty acids — is absorbed by intestinal cells, which use it as fuel.
But the gut’s microbes do more than just make energy. They also send messages.
Intestinal cells rely on chemical signals from the bacteria to work properly, Dr. Gewirtz said. The cells respond to the signals by multiplying and making a healthy supply of mucus. They also release bacteria-killing molecules.
By generating these responses, gut bacteria help maintain a peaceful coexistence with the immune system. They rest atop the gut’s mucus layer at a safe distance from the intestinal wall. Any bacteria that wind up too close get wiped out by antimicrobial poisons.
While some species of gut bacteria feed directly on dietary fiber, they probably support other species that feed on their waste. A number of species in this ecosystem — all of it built on fiber — may be talking to our guts.
Going on a low-fiber diet disturbs this peaceful relationship, the new studies suggest. The species that depend on dietary fiber starve, as do the other species that depend on them. Some species may switch to feeding on the host’s own mucus.
With less fuel, intestinal cells grow more slowly. And without a steady stream of chemical signals from bacteria, the cells slow their production of mucus and bacteria-killing poisons.
As a result, bacteria edge closer to the intestinal wall, and the immune system kicks into high gear.
... Among other things, chronic inflammation may interfere with how the body uses the calories in food, storing more of it as fat rather than burning it for energy.
Justin L. Sonnenburg, a biologist at Stanford University who was not involved in the new studies, said that a low-fiber diet can cause low-level inflammation not only in the gut, but throughout the body.
His research suggests that when bacteria break down dietary fiber down into short-chain fatty acids, some of them pass into the bloodstream and travel to other organs, where they act as signals to quiet down the immune system.
Hannah D. Holscher, a nutrition scientist at the University of Illinois... provide(s) volunteers with all their meals for two weeks. She can then give some of her volunteers an extra source of fiber — such as walnuts — and look for changes in both their microbiome and their levels of inflammation.
Dr. Holscher and other researchers hope that they will learn enough about how fiber influences the microbiome to use it as a way to treat disorders. Lowering inflammation with fiber may also help in the treatment of immune disorders such as inflammatory bowel disease.
Fiber may also help reverse obesity. Last month in the American Journal of Clinical Nutrition, Dr. Holscher and her colleagues reviewed a number of trials in which fiber was used to treat obesity. They found that fiber supplements helped obese people to lose about five pounds, on average.
But for those who want to stay healthy, simply adding one kind of fiber to a typical Western diet won’t be a panacea. Giving mice inulin in the new studies only partly restored them to health.
That’s probably because we depend on a number of different kinds of dietary fiber we get from plants. It’s possible that each type of fiber feeds a particular set of bacteria, which send their own important signals to our bodies...
https://www.nytimes.com/2018/01/01/science/food-fiber-microbiome-inflammation.ht...
The inulin in study is widely available in pharmacies as a generic brand powder. (Made from chicory root.) Some gut conditions aggravated by soluble fiber, so do your homework. Increase gradually in diet, so you don't overstrip your microbiome and cause GIT distress. (I mix another soluble fiber in my coffee every morning (gum Arabic, Heather's).)
Variety of fibers best: fruits & veg, whole grains (like oatmeal), beans, etc. Plus the soluble fiber supplement? http://healthyeating.sfgate.com/sources-soluble-fiber-natural-foods-2125.html Also--probiotics like kefir
NYT article that follows Thomson et al. has great explanation of how fiber feeds microbiome that effects these effects and more:
Sharon V Thomson et al. 2017. Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. First published November 1, 2017, doi: 10.3945/ajcn.117.163246. http://ajcn.nutrition.org/content/early/2017/11/01/ajcn.117.163246.abstract
Abstract
Background: There is strong epidemiologic evidence that dietary fiber intake is protective against overweight and obesity; however, results of intervention studies have been mixed. Soluble fiber beneficially affects metabolism, and fiber supplementation may be a feasible approach to improve body composition and glycemia in adults with overweight and obesity.
Objective: We evaluated randomized controlled trials (RCTs) of isolated soluble fiber supplementation in overweight and obese adults on outcomes related to weight management (body mass index (BMI; in kg/m2), body weight, percentage of body fat, and waist circumference)and glucose and insulin metabolism (homeostasis model assessment of insulin resistance and fasting insulin) through a systematic review and meta-analysis.
Design: We searched PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Cochrane Library databases. Eligible studies were RCTs that compared isolated soluble fiber with placebo treatments without energy-restriction protocols...
Results: Findings from 12 RCTs (n = 609 participants) from 2 to 17 wk of duration are summarized in this review. Soluble fiber supplementation reduced BMI by 0.84...body weight by 2.52 kg...body fat by 0.41%...fasting glucose by 0.17 mmol/L...and fasting insulin by 15.88 pmol/L... compared with the effects of placebo treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes.
Conclusions: Isolated soluble fiber supplementation improves anthropometric and metabolic outcomes in overweight and obese adults, thereby indicating that supplementation may improve fiber intake and health in these individuals. However, the interpretation of these findings warrants caution because of the considerable between-study heterogeneity...
_______________________________________________________________________
Fiber Is Good for You. Now Scientists May Know Why.
Carl Zimmer | JAN. 1, 2018
A diet of fiber-rich foods, such as fruits and vegetables, reduces the risk of developing diabetes, heart disease and arthritis. Indeed, the evidence for fiber’s benefits extends beyond any particular ailment: Eating more fiber seems to lower people’s mortality rate, whatever the cause.
...But while the benefits are clear, it’s not so clear why fiber is so great.
,,,The ability of these bacteria to survive on fiber we can’t digest ourselves has led many experts to wonder if the microbes are somehow involved in the benefits of the fruits-and-vegetables diet. Two detailed studies published recently in the journal Cell Host and Microbe provide compelling evidence that the answer is yes.
In one experiment, Andrew T. Gewirtz of Georgia State University and his colleagues put mice on a low-fiber, high-fat diet. By examining fragments of bacterial DNA in the animals’ feces, the scientists were able to estimate the size of the gut bacterial population in each mouse.
On a low-fiber diet, they found, the population crashed, shrinking tenfold.
Dr. Bäckhed and his colleagues carried out a similar experiment, surveying the microbiome in mice as they were switched from fiber-rich food to a low-fiber diet. “It’s basically what you’d get at McDonald’s,” said Dr. Bäckhed said. “A lot of lard, a lot of sugar, and twenty percent protein.”
The scientists focused on the diversity of species that make up the mouse’s gut microbiome. Shifting the animals to a low-fiber diet had a dramatic effect, they found: Many common species became rare, and rare species became common.
Along with changes to the microbiome, both teams also observed rapid changes to the mice themselves. Their intestines got smaller, and its mucus layer thinner. As a result, bacteria wound up much closer to the intestinal wall, and that encroachment triggered an immune reaction.
After a few days on the low-fiber diet, mouse intestines developed chronic inflammation. After a few weeks, Dr. Gewirtz’s team observed that the mice began to change in other ways, putting on fat, for example, and developing higher blood sugar levels.
Dr. Bäckhed and his colleagues also fed another group of rodents the high-fat menu, along with a modest dose of a type of fiber called inulin. The mucus layer in their guts was healthier than in mice that didn’t get fiber, the scientists found, and intestinal bacteria were kept at a safer distance from their intestinal wall.
Dr. Gewirtz and his colleagues gave inulin to their mice as well, but at a much higher dose. The improvements were even more dramatic: Despite a high-fat diet, the mice had healthy populations of bacteria in their guts, their intestines were closer to normal, and they put on less weight.
Dr. Bäckhed and his colleagues ran one more interesting experiment: They spiked water given to mice on a high-fat diet with a species of fiber-feeding bacteria. The addition changed the mice for the better: Even on a high-fat diet, they produced more mucus in their guts, creating a healthy barrier to keep bacteria from the intestinal walls.
One way that fiber benefits health is by giving us, indirectly, another source of food, Dr. Gewirtz said. Once bacteria are done harvesting the energy in dietary fiber, they cast off the fragments as waste. That waste — in the form of short-chain fatty acids — is absorbed by intestinal cells, which use it as fuel.
But the gut’s microbes do more than just make energy. They also send messages.
Intestinal cells rely on chemical signals from the bacteria to work properly, Dr. Gewirtz said. The cells respond to the signals by multiplying and making a healthy supply of mucus. They also release bacteria-killing molecules.
By generating these responses, gut bacteria help maintain a peaceful coexistence with the immune system. They rest atop the gut’s mucus layer at a safe distance from the intestinal wall. Any bacteria that wind up too close get wiped out by antimicrobial poisons.
While some species of gut bacteria feed directly on dietary fiber, they probably support other species that feed on their waste. A number of species in this ecosystem — all of it built on fiber — may be talking to our guts.
Going on a low-fiber diet disturbs this peaceful relationship, the new studies suggest. The species that depend on dietary fiber starve, as do the other species that depend on them. Some species may switch to feeding on the host’s own mucus.
With less fuel, intestinal cells grow more slowly. And without a steady stream of chemical signals from bacteria, the cells slow their production of mucus and bacteria-killing poisons.
As a result, bacteria edge closer to the intestinal wall, and the immune system kicks into high gear.
... Among other things, chronic inflammation may interfere with how the body uses the calories in food, storing more of it as fat rather than burning it for energy.
Justin L. Sonnenburg, a biologist at Stanford University who was not involved in the new studies, said that a low-fiber diet can cause low-level inflammation not only in the gut, but throughout the body.
His research suggests that when bacteria break down dietary fiber down into short-chain fatty acids, some of them pass into the bloodstream and travel to other organs, where they act as signals to quiet down the immune system.
Hannah D. Holscher, a nutrition scientist at the University of Illinois... provide(s) volunteers with all their meals for two weeks. She can then give some of her volunteers an extra source of fiber — such as walnuts — and look for changes in both their microbiome and their levels of inflammation.
Dr. Holscher and other researchers hope that they will learn enough about how fiber influences the microbiome to use it as a way to treat disorders. Lowering inflammation with fiber may also help in the treatment of immune disorders such as inflammatory bowel disease.
Fiber may also help reverse obesity. Last month in the American Journal of Clinical Nutrition, Dr. Holscher and her colleagues reviewed a number of trials in which fiber was used to treat obesity. They found that fiber supplements helped obese people to lose about five pounds, on average.
But for those who want to stay healthy, simply adding one kind of fiber to a typical Western diet won’t be a panacea. Giving mice inulin in the new studies only partly restored them to health.
That’s probably because we depend on a number of different kinds of dietary fiber we get from plants. It’s possible that each type of fiber feeds a particular set of bacteria, which send their own important signals to our bodies...
https://www.nytimes.com/2018/01/01/science/food-fiber-microbiome-inflammation.ht...
13margd
Cilia in the brain may be busier than previously thought
The long-overlooked nerve cell appendage may help prevent obesity or aid communication among cells
Laura Sanders | January 19, 2018
...cilia appear to play a role in preventing obesity, researchers report January 8 in three studies in Nature Genetics
...molecular geneticist Christian Vaisse of the University of California, San Francisco... studied mutations in a protein called MC4R that are known to cause severe obesity in people. Experiments on mice showed that MC4R normally resides within the cilia on appetite-controlling nerve cells. But several of these mutations prevented MC4R from reaching those cells’ cilia from elsewhere in the cells, experiments on cells in dishes showed. And one of these mutations prevented MC4R from reaching nerve cell cilia in the brains of mice.
When the researchers interfered with ADCY3, a protein in the cilia that helps MC4R regulate appetite, the resulting mice became obese. Those results suggest that MC4R must reach the cilia in order to interact with ADCY3 and work properly. In the other two papers, scientists link the ADCY3 gene to obesity in people, providing more evidence that cilia are involved in obesity.
...That link has already been found in rare cases. Mutations that affect cilia can cause severe obesity, as seen with diseases such as Bardet-Biedl syndrome. But the new results hint that abnormal cilia may be more widely involved in obesity. Earlier genetic studies have tied obesity to the MC4R gene, which the mouse study now shows to be important in cilia. It’s possible that many of the common genetic obesity culprits may actually be tinkering with the primary cilia, Vaisse says.
It’s not yet clear why the MC4R protein needs to reach the cilia to control appetite, (Kirk Mykytyn, a cell biologist at Ohio State University College of Medicine in Columbus) says. It’s possible that the appendages possess the right mix of helper proteins that aid MC4R in its job. Or cilia might change the way the protein works, allowing it to be more efficient....
Citations
J.E. Siljee et al. Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nature Genetics. Published online January 8, 2018. doi: 10.1038/s41588-017-0020-9. https://www.nature.com/articles/s41588-017-0020-9.epdf
N. Grarup et al. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nature Genetics. Published online January 8, 2018. doi:10.1038/s41588-017-0022-7. https://www.nature.com/articles/s41588-017-0022-7.epdf
S. Saeed et al. Loss-of-function mutations in ADCY3 cause monogenic severe obesity. Nature Genetics. Published online January 8, 2018. doi:10.1038/s41588-017-0023-6. https://www.nature.com/articles/s41588-017-0023-6.epdf
...
https://www.sciencenews.org/article/cilia-brain-may-be-busier-previously-thought
The long-overlooked nerve cell appendage may help prevent obesity or aid communication among cells
Laura Sanders | January 19, 2018
...cilia appear to play a role in preventing obesity, researchers report January 8 in three studies in Nature Genetics
...molecular geneticist Christian Vaisse of the University of California, San Francisco... studied mutations in a protein called MC4R that are known to cause severe obesity in people. Experiments on mice showed that MC4R normally resides within the cilia on appetite-controlling nerve cells. But several of these mutations prevented MC4R from reaching those cells’ cilia from elsewhere in the cells, experiments on cells in dishes showed. And one of these mutations prevented MC4R from reaching nerve cell cilia in the brains of mice.
When the researchers interfered with ADCY3, a protein in the cilia that helps MC4R regulate appetite, the resulting mice became obese. Those results suggest that MC4R must reach the cilia in order to interact with ADCY3 and work properly. In the other two papers, scientists link the ADCY3 gene to obesity in people, providing more evidence that cilia are involved in obesity.
...That link has already been found in rare cases. Mutations that affect cilia can cause severe obesity, as seen with diseases such as Bardet-Biedl syndrome. But the new results hint that abnormal cilia may be more widely involved in obesity. Earlier genetic studies have tied obesity to the MC4R gene, which the mouse study now shows to be important in cilia. It’s possible that many of the common genetic obesity culprits may actually be tinkering with the primary cilia, Vaisse says.
It’s not yet clear why the MC4R protein needs to reach the cilia to control appetite, (Kirk Mykytyn, a cell biologist at Ohio State University College of Medicine in Columbus) says. It’s possible that the appendages possess the right mix of helper proteins that aid MC4R in its job. Or cilia might change the way the protein works, allowing it to be more efficient....
Citations
J.E. Siljee et al. Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nature Genetics. Published online January 8, 2018. doi: 10.1038/s41588-017-0020-9. https://www.nature.com/articles/s41588-017-0020-9.epdf
N. Grarup et al. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nature Genetics. Published online January 8, 2018. doi:10.1038/s41588-017-0022-7. https://www.nature.com/articles/s41588-017-0022-7.epdf
S. Saeed et al. Loss-of-function mutations in ADCY3 cause monogenic severe obesity. Nature Genetics. Published online January 8, 2018. doi:10.1038/s41588-017-0023-6. https://www.nature.com/articles/s41588-017-0023-6.epdf
...
https://www.sciencenews.org/article/cilia-brain-may-be-busier-previously-thought
14margd
Counting Calories Is Not the Key to Weight Loss, New Study Finds
ANAHAD O’CONNOR | FEB. 20, 2018
...a new study, published Tuesday in JAMA...found that people who cut back on added sugar, refined grains and highly processed foods while concentrating on eating plenty of vegetables and whole foods — without worrying about counting calories or limiting portion sizes — lost significant amounts of weight over the course of a year.
The strategy worked for people whether they followed diets that were mostly low in fat or mostly low in carbohydrates. And their success did not appear to be influenced by their genetics or their insulin-response to carbohydrates, a finding that casts doubt on the increasingly popular idea that different diets should be recommended to people based on their DNA makeup or on their tolerance for carbs or fat.
The research lends strong support to the notion that diet quality, not quantity, is what helps people lose and manage their weight most easily in the long run. It also suggests that health authorities should shift away from telling the public to obsess over calories and instead encourage Americans to avoid processed foods that are made with refined starches and added sugar, like bagels, white bread, refined flour and sugary snacks and beverages
...Soft drinks, fruit juice, muffins, white rice and white bread are technically low in fat, for example, but the low-fat group was told to avoid those things and eat foods like brown rice, barley, steel-cut oats, lentils, lean meats, low-fat dairy products, quinoa, fresh fruit and legumes. The low-carb group was trained to choose nutritious foods like olive oil, salmon, avocados, hard cheeses, vegetables, nut butters, nuts and seeds, and grass-fed and pasture-raised animal foods.
...While people on average lost a significant amount of weight in the study, there was also wide variability in both groups. Some people gained weight, and some lost as much as 50 to 60 pounds. Dr. Gardner said that the people who lost the most weight reported that the study had “changed their relationship with food.” They no longer ate in their cars or in front of their television screens, and they were cooking more at home and sitting down to eat dinner with their families, for example.
... the new study found that after one year of focusing on food quality, not calories, the two groups lost substantial amounts of weight. On average, the members of the low-carb group lost just over 13 pounds, while those in the low-fat group lost about 11.7 pounds. Both groups also saw improvements in other health markers, like reductions in their waist sizes, body fat, and blood sugar and blood pressure levels.
...focus on that foundational diet, which is more vegetables, more whole foods, less added sugar and less refined grains.”
https://www.nytimes.com/2018/02/20/well/eat/counting-calories-weight-loss-diet-d...
__________________________________________________________________________________
Christopher D. Gardner et al. February 20, 2018. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion. JAMA. 2018;319(7):667-679. doi:10.1001/jama.2018.0245
https://jamanetwork.com/journals/jama/article-abstract/2673150?redirect=true
Key Points
Question What is the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change at 12 months and are these effects related to genotype pattern or insulin secretion?
Findings In this randomized clinical trial among 609 overweight adults, weight change over 12 months was not significantly different for participants in the HLF diet group (−5.3 kg) vs the HLC diet group (−6.0 kg), and there was no significant diet-genotype interaction or diet-insulin interaction with 12-month weight loss.
Meaning There was no significant difference in 12-month weight loss between the HLF and HLC diets, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss.
ANAHAD O’CONNOR | FEB. 20, 2018
...a new study, published Tuesday in JAMA...found that people who cut back on added sugar, refined grains and highly processed foods while concentrating on eating plenty of vegetables and whole foods — without worrying about counting calories or limiting portion sizes — lost significant amounts of weight over the course of a year.
The strategy worked for people whether they followed diets that were mostly low in fat or mostly low in carbohydrates. And their success did not appear to be influenced by their genetics or their insulin-response to carbohydrates, a finding that casts doubt on the increasingly popular idea that different diets should be recommended to people based on their DNA makeup or on their tolerance for carbs or fat.
The research lends strong support to the notion that diet quality, not quantity, is what helps people lose and manage their weight most easily in the long run. It also suggests that health authorities should shift away from telling the public to obsess over calories and instead encourage Americans to avoid processed foods that are made with refined starches and added sugar, like bagels, white bread, refined flour and sugary snacks and beverages
...Soft drinks, fruit juice, muffins, white rice and white bread are technically low in fat, for example, but the low-fat group was told to avoid those things and eat foods like brown rice, barley, steel-cut oats, lentils, lean meats, low-fat dairy products, quinoa, fresh fruit and legumes. The low-carb group was trained to choose nutritious foods like olive oil, salmon, avocados, hard cheeses, vegetables, nut butters, nuts and seeds, and grass-fed and pasture-raised animal foods.
...While people on average lost a significant amount of weight in the study, there was also wide variability in both groups. Some people gained weight, and some lost as much as 50 to 60 pounds. Dr. Gardner said that the people who lost the most weight reported that the study had “changed their relationship with food.” They no longer ate in their cars or in front of their television screens, and they were cooking more at home and sitting down to eat dinner with their families, for example.
... the new study found that after one year of focusing on food quality, not calories, the two groups lost substantial amounts of weight. On average, the members of the low-carb group lost just over 13 pounds, while those in the low-fat group lost about 11.7 pounds. Both groups also saw improvements in other health markers, like reductions in their waist sizes, body fat, and blood sugar and blood pressure levels.
...focus on that foundational diet, which is more vegetables, more whole foods, less added sugar and less refined grains.”
https://www.nytimes.com/2018/02/20/well/eat/counting-calories-weight-loss-diet-d...
__________________________________________________________________________________
Christopher D. Gardner et al. February 20, 2018. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion. JAMA. 2018;319(7):667-679. doi:10.1001/jama.2018.0245
https://jamanetwork.com/journals/jama/article-abstract/2673150?redirect=true
Key Points
Question What is the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change at 12 months and are these effects related to genotype pattern or insulin secretion?
Findings In this randomized clinical trial among 609 overweight adults, weight change over 12 months was not significantly different for participants in the HLF diet group (−5.3 kg) vs the HLC diet group (−6.0 kg), and there was no significant diet-genotype interaction or diet-insulin interaction with 12-month weight loss.
Meaning There was no significant difference in 12-month weight loss between the HLF and HLC diets, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss.
15margd
How obesity makes it harder to taste
Inflammation linked to the disease caused the loss of taste buds in mice
Aimee Cunningham | March 20, 2018
...Compared with siblings that were fed normal mouse chow, mice given high-fat meals lost about 25 percent of their taste buds over eight weeks. Buds went missing because mature taste bud cells died off more quickly, and fewer new cells developed to take their place. Chronic, low-level inflammation associated with obesity appears to be behind the loss.
...The taste tissues of the obese mice had a higher amount of a type of protein called a cytokine, which regulates inflammation, than their normal-weight kin...
This particular cytokine, called tumor necrosis factor alpha, seems to be damaging to taste buds...
Citations
A. Kaufman et al. Inflammation arising from obesity reduces taste bud abundance and inhibits renewal. PLOS Biology. Published online March 20, 2018. doi: 10.1371/journal.pbio.2001959. http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2001959
Further Reading
L. Sanders. Obscure brain region linked to feeding frenzy in mice. Science News Online, May 25, 2017. https://www.sciencenews.org/article/obscure-brain-region-linked-feeding-frenzy-m...
B. Brookshire. The need to feed and eating for pleasure are inextricably linked. Science News Online, August 27, 2015. https://www.sciencenews.org/blog/scicurious/need-feed-and-eating-pleasure-are-in...
https://www.sciencenews.org/article/how-obesity-makes-it-harder-taste
Inflammation linked to the disease caused the loss of taste buds in mice
Aimee Cunningham | March 20, 2018
...Compared with siblings that were fed normal mouse chow, mice given high-fat meals lost about 25 percent of their taste buds over eight weeks. Buds went missing because mature taste bud cells died off more quickly, and fewer new cells developed to take their place. Chronic, low-level inflammation associated with obesity appears to be behind the loss.
...The taste tissues of the obese mice had a higher amount of a type of protein called a cytokine, which regulates inflammation, than their normal-weight kin...
This particular cytokine, called tumor necrosis factor alpha, seems to be damaging to taste buds...
Citations
A. Kaufman et al. Inflammation arising from obesity reduces taste bud abundance and inhibits renewal. PLOS Biology. Published online March 20, 2018. doi: 10.1371/journal.pbio.2001959. http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2001959
Further Reading
L. Sanders. Obscure brain region linked to feeding frenzy in mice. Science News Online, May 25, 2017. https://www.sciencenews.org/article/obscure-brain-region-linked-feeding-frenzy-m...
B. Brookshire. The need to feed and eating for pleasure are inextricably linked. Science News Online, August 27, 2015. https://www.sciencenews.org/blog/scicurious/need-feed-and-eating-pleasure-are-in...
https://www.sciencenews.org/article/how-obesity-makes-it-harder-taste
16margd
Good news: pasta linked to weight loss, when served in 1/2 c servings 3X daily. Apparently due to its low glycemic index.
(In attempt to maximize insoluble fiber in diet, I've been exploring pasta made from legumes. Most recently, DH used a chickpea tortellini--Banza brand--to make a pasta salad for a road trip. Yum! Though Banza isn't particularly cheap...)
Laura Chiavaroli et al. 2018. Effect of pasta in the context of low-glycaemic index dietary patterns on body weight and markers of adiposity: a systematic review and meta-analysis of randomised controlled trials in adults. BMJ Volume 8, Issue 3. http://bmjopen.bmj.com/content/8/3/e019438
Conclusions Pasta in the context of low-GI dietary patterns does not adversely affect adiposity and even reduces body weight and BMI compared with higher-GI dietary patterns. Future trials should assess the effect of pasta in the context of other ‘healthy’ dietary patterns.
_________________________________________________
Eating Pasta Linked to Weight Loss in New Study
Kashmira Gander | 4/3/18
http://www.newsweek.com/pasta-weight-loss-869178
...The study emphasized that the inclusion of whole grains does not significantly affect pasta's GI status. And while it is relatively low in fiber, pasta has a similar GI rating to fiber-rich foods such as barley, legumes and steel cut oats, and a lower rating than wholewheat bread, breakfast cereals like bran flakes and potatoes with skin. On average, white pasta also has a higher micronutrient content than other white wheat products...
(In attempt to maximize insoluble fiber in diet, I've been exploring pasta made from legumes. Most recently, DH used a chickpea tortellini--Banza brand--to make a pasta salad for a road trip. Yum! Though Banza isn't particularly cheap...)
Laura Chiavaroli et al. 2018. Effect of pasta in the context of low-glycaemic index dietary patterns on body weight and markers of adiposity: a systematic review and meta-analysis of randomised controlled trials in adults. BMJ Volume 8, Issue 3. http://bmjopen.bmj.com/content/8/3/e019438
Conclusions Pasta in the context of low-GI dietary patterns does not adversely affect adiposity and even reduces body weight and BMI compared with higher-GI dietary patterns. Future trials should assess the effect of pasta in the context of other ‘healthy’ dietary patterns.
_________________________________________________
Eating Pasta Linked to Weight Loss in New Study
Kashmira Gander | 4/3/18
http://www.newsweek.com/pasta-weight-loss-869178
...The study emphasized that the inclusion of whole grains does not significantly affect pasta's GI status. And while it is relatively low in fiber, pasta has a similar GI rating to fiber-rich foods such as barley, legumes and steel cut oats, and a lower rating than wholewheat bread, breakfast cereals like bran flakes and potatoes with skin. On average, white pasta also has a higher micronutrient content than other white wheat products...
172wonderY
The new film 'I Feel Pretty' addresses female body image.
Film review:
Review: ‘I Feel Pretty’ Doesn’t Even Go Skin Deep
"The idea that a lack of self-confidence can be essentially bootstrapped away — that all we need to combat oppressive forces is the power of positive thinking and a flattering lipstick — is an exhausted, false fairy tale, one peddled by (among others!) self-help books, beauty companies and, disappointingly, movies like this one."
Commentary:
‘I Feel Pretty’ and the Rise of Beauty-Standard Denialism
"The movie suggests that the only thing holding back regular-looking women is their belief that looking regular holds them back at all. That attitude puts the onus on individual women to improve their self-esteem instead of criticizing societal beauty standards writ large. The reality is that expectations for female appearances have never been higher. It’s just become taboo to admit that."
Reader opinions:
A Woman’s Beauty: Who Gets to Decide?
Film review:
Review: ‘I Feel Pretty’ Doesn’t Even Go Skin Deep
"The idea that a lack of self-confidence can be essentially bootstrapped away — that all we need to combat oppressive forces is the power of positive thinking and a flattering lipstick — is an exhausted, false fairy tale, one peddled by (among others!) self-help books, beauty companies and, disappointingly, movies like this one."
Commentary:
‘I Feel Pretty’ and the Rise of Beauty-Standard Denialism
"The movie suggests that the only thing holding back regular-looking women is their belief that looking regular holds them back at all. That attitude puts the onus on individual women to improve their self-esteem instead of criticizing societal beauty standards writ large. The reality is that expectations for female appearances have never been higher. It’s just become taboo to admit that."
Reader opinions:
A Woman’s Beauty: Who Gets to Decide?
18margd
Best results for reducing volume of food consumed: use 10" plates and turn tv off for dinner. Eight other behavioral changes rated for compliance and weight loss in Table 1. Looks like some might be more effective if employed more frequently.
Brian Wansink, David R. Just, and Collin R. Payne. 2009. Mindless Eating and Healthy Heuristics for the Irrational. American Economic Review: Papers & Proceedings 2009, 99:2, 165–169. http://www.aeaweb.org/articles.php?doi . http://www.indiana.edu/~abcwest/pmwiki/CAFE/wansink,just,payne.mindless.eating.h...
Brian Wansink, David R. Just, and Collin R. Payne. 2009. Mindless Eating and Healthy Heuristics for the Irrational. American Economic Review: Papers & Proceedings 2009, 99:2, 165–169. http://www.aeaweb.org/articles.php?doi . http://www.indiana.edu/~abcwest/pmwiki/CAFE/wansink,just,payne.mindless.eating.h...
19margd
Cell Metabolism, DiFeliceantonio and Coppin et al.: "Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward" https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30325-5 , DOI: 10.1016/j.cmet.2018.05.018 . https://www.sciencedirect.com/science/article/pii/S1550413118303255
Highlights
• Fat and carbohydrate interact to potentiate reward independently of liking
• This is reflected in supra-additive responses in the striatum during food valuation
• Participants are able to estimate energy density from fat, but not carbohydrate
• Accurate estimation of energy density recruits a prefrontal-fusiform gyrus circuit
_____________________________________________________________________
Foods combining fats and carbohydrates more rewarding than foods with just fats or carbs
Cell Press | June 14, 2018
...Researchers show that the reward center of the brain values foods high in both fat and carbohydrates—i.e., many processed foods—more than foods containing only fat or only carbs. A study of 206 adults, to appear June 14 in the journal Cell Metabolism, supports the idea that these kinds of foods hijack our body's inborn signals governing food consumption.
...After the domestication of plants and animals and the development of grain and dairy production around 12,000 years ago, opportunities to consume fat and carbohydrates together increased, but processed foods like donuts, which could contain 11 grams of fat and 17 grams of carbohydrate, have only been around for 150 years, not long enough for us to evolve a new brain response to them.
Scientists believe our past experience with the nutritive properties of carbohydrates releases dopamine in the brain through an as-yet-unknown metabolic signal. These kinds of signals seem to help regulate what and how much we eat.
The researchers theorize that the simultaneous activation of fat and carbohydrate signaling pathways launches an effect that human physiology has not evolved to handle. Consistent with this suggestion, rodents given access to fat alone or carbohydrate alone regulate their total daily caloric intake and body weight. But given unrestricted access to fat and carbohydrates, they quickly gain weight.
https://medicalxpress.com/news/2018-06-foods-combining-fats-carbohydrates-reward...
Highlights
• Fat and carbohydrate interact to potentiate reward independently of liking
• This is reflected in supra-additive responses in the striatum during food valuation
• Participants are able to estimate energy density from fat, but not carbohydrate
• Accurate estimation of energy density recruits a prefrontal-fusiform gyrus circuit
_____________________________________________________________________
Foods combining fats and carbohydrates more rewarding than foods with just fats or carbs
Cell Press | June 14, 2018
...Researchers show that the reward center of the brain values foods high in both fat and carbohydrates—i.e., many processed foods—more than foods containing only fat or only carbs. A study of 206 adults, to appear June 14 in the journal Cell Metabolism, supports the idea that these kinds of foods hijack our body's inborn signals governing food consumption.
...After the domestication of plants and animals and the development of grain and dairy production around 12,000 years ago, opportunities to consume fat and carbohydrates together increased, but processed foods like donuts, which could contain 11 grams of fat and 17 grams of carbohydrate, have only been around for 150 years, not long enough for us to evolve a new brain response to them.
Scientists believe our past experience with the nutritive properties of carbohydrates releases dopamine in the brain through an as-yet-unknown metabolic signal. These kinds of signals seem to help regulate what and how much we eat.
The researchers theorize that the simultaneous activation of fat and carbohydrate signaling pathways launches an effect that human physiology has not evolved to handle. Consistent with this suggestion, rodents given access to fat alone or carbohydrate alone regulate their total daily caloric intake and body weight. But given unrestricted access to fat and carbohydrates, they quickly gain weight.
https://medicalxpress.com/news/2018-06-foods-combining-fats-carbohydrates-reward...
20pmackey
>18 margd: Thanks for this post, margd. This is actually helpful. I'm prediabetic and struggle to improve my eating habits. The suggestions in the article will help. According to this, I need to stop eating Monday night dinner while watching my Westworld recording. :(
21margd
>20 pmackey: Soluble fiber might help stave off diabetes--oatmeal, legumes, reheated potatoes, etc. Maybe try powdered soluble fiber in your morning coffee (like a creamer only tasteless) to help you approach the 37 grams found effective below. (Increase GRADUALLY to this level.) Inulin powder mentioned below is widely available in pharmacies--store brands even. Maybe other soluble fiber powders as well. Heather's Tummy Fiber (gum of Acacia senegal) is available online.
Might be worth buying a glucose monitor: easier to stay with new eating habits if improvements show up every morning before breakfast!
Enlisting Gut Bacteria And Fiber To Fight Diabetes
Brenda Goodman | March 9, 2018
...Could High-Fiber Diets Stave Off Diabetes?
...27 people with type 2 diabetes on a very high-fiber diet ... followed...for 12 weeks, measuring changes to their blood sugar, and also to their gut bacteria.
They compared this group with 16 others who also had type 2 diabetes who got standard advice on exercise and eating right for diabetes along with a diet for the study that racked up roughly same number of calories, but had a lot less fiber.
The high-fiber group was getting a whopping 37 grams of fiber a day, while the group getting the average, healthy diet was eating about 16 grams of fiber a day -- which, by chance, is about what American adults average.
Both groups were also taking a medication called acarbose to help manage their blood sugar. Acarbose acts a bit like fiber in that it prevents some carbohydrates from being digested in the gut for energy. Before the study, all participants were weaned off any other medications to manage their blood sugar. If they used insulin, it was adjusted as needed throughout the study.
Both groups improved, but by the end of the experiment, the group on the very high-fiber diet was healthier than the group getting standard care. They had better control of their blood sugar, and they’d lost a bit more weight. About 90% of the high-fiber group achieved good control of their blood sugar -- keeping their hemoglobin A1c under 7%, the target recommended by the American Diabetes Association -- compared with just 50% of the group on a standard diabetes diet.
Here’s why that could be true.
All that fiber, which came from a wide variety of food sources, fertilized the growth of 15 strains of bacteria that produce certain short-chain fatty acids. Those acids act as both a fuel source for cells and as messengers.
In the new study, these short-chain fatty acids signaled the gut to make more glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).
GLP-1 is a hormone that tells the body to make more insulin, while PYY dials down appetite. The two are critical in keeping blood sugar and weight under control.
Some diabetes drugs also work by increasing GLP-1. The increase in short-chain fatty acids also made the gut walls unfriendly to other kinds of bacteria that block GLP-1, boosting the effect.
“This is one benefit, one reason why high-fiber diets work,” says study researcher Liping Zhao, PhD, a professor of applied microbiology at both Rutgers University in New Brunswick, NJ, and Shanghai Jiao Tong University in Shanghai, China.
To make sure it was the change in gut bacteria that was driving the results -- and not something else -- the scientists then transferred the gut bacteria from their study participants to mice that were bred to be germ-free. Because they were bred not to have any of their own gut bacteria, scientists could later introduce bacteria and watch what happened as they started growing.
The mice that got the bacteria from the humans on the high-fiber diets had better fasting blood sugar levels than mice that got bacteria from people on the usual diabetes diet, even though they were eating the same chow.
The study was published in the journal Science.
Getting More Daily Fiber
The study authors say it would be difficult for the average person to copy their high-fiber diet. People in the high-fiber part of the study ate a specially prepared gruel made from oats, white beans, yellow corn, red beans, yams, peanuts, and lotus seeds, along with two whole grains that are unfamiliar to Westerners -- green buckwheat and adlay, or Job’s tears. They also got more fiber in the form of powders that included bitter melon, kudzu starch, inulin, and resistant dextrin...
https://www.webmd.com/diabetes/news/20180309/enlisting-gut-bacteria-and-fiber-to...
________________________________________________________
Rutgers University. "Fiber-fermenting bacteria improve health of type 2 diabetes patients: Dietary fibers promote gut bacteria that benefit blood glucose control." ScienceDaily. ScienceDaily, 8 March 2018.
________________________________________________________
Liping Zhao, Feng Zhang, Xiaoying Ding, Guojun Wu, Yan Y. Lam, Xuejiao Wang, Huaqing Fu, Xinhe Xue, Chunhua Lu, Jilin Ma, Lihua Yu, Chengmei Xu, Zhongying Ren, Ying Xu, Songmei Xu, Hongli Shen, Xiuli Zhu, Yu Shi, Qingyun Shen, Weiping Dong, Rui Liu, Yunxia Ling, Yue Zeng, Xingpeng Wang, Qianpeng Zhang, Jing Wang, Linghua Wang, Yanqiu Wu, Benhua Zeng, Hong Wei, Menghui Zhang, Yongde Peng, Chenhong Zhang. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 2018; 359 (6380): 1151 DOI: 10.1126/science.aao5774
http://science.sciencemag.org/content/359/6380/1151
________________________________________________________
Might be worth buying a glucose monitor: easier to stay with new eating habits if improvements show up every morning before breakfast!
Enlisting Gut Bacteria And Fiber To Fight Diabetes
Brenda Goodman | March 9, 2018
...Could High-Fiber Diets Stave Off Diabetes?
...27 people with type 2 diabetes on a very high-fiber diet ... followed...for 12 weeks, measuring changes to their blood sugar, and also to their gut bacteria.
They compared this group with 16 others who also had type 2 diabetes who got standard advice on exercise and eating right for diabetes along with a diet for the study that racked up roughly same number of calories, but had a lot less fiber.
The high-fiber group was getting a whopping 37 grams of fiber a day, while the group getting the average, healthy diet was eating about 16 grams of fiber a day -- which, by chance, is about what American adults average.
Both groups were also taking a medication called acarbose to help manage their blood sugar. Acarbose acts a bit like fiber in that it prevents some carbohydrates from being digested in the gut for energy. Before the study, all participants were weaned off any other medications to manage their blood sugar. If they used insulin, it was adjusted as needed throughout the study.
Both groups improved, but by the end of the experiment, the group on the very high-fiber diet was healthier than the group getting standard care. They had better control of their blood sugar, and they’d lost a bit more weight. About 90% of the high-fiber group achieved good control of their blood sugar -- keeping their hemoglobin A1c under 7%, the target recommended by the American Diabetes Association -- compared with just 50% of the group on a standard diabetes diet.
Here’s why that could be true.
All that fiber, which came from a wide variety of food sources, fertilized the growth of 15 strains of bacteria that produce certain short-chain fatty acids. Those acids act as both a fuel source for cells and as messengers.
In the new study, these short-chain fatty acids signaled the gut to make more glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).
GLP-1 is a hormone that tells the body to make more insulin, while PYY dials down appetite. The two are critical in keeping blood sugar and weight under control.
Some diabetes drugs also work by increasing GLP-1. The increase in short-chain fatty acids also made the gut walls unfriendly to other kinds of bacteria that block GLP-1, boosting the effect.
“This is one benefit, one reason why high-fiber diets work,” says study researcher Liping Zhao, PhD, a professor of applied microbiology at both Rutgers University in New Brunswick, NJ, and Shanghai Jiao Tong University in Shanghai, China.
To make sure it was the change in gut bacteria that was driving the results -- and not something else -- the scientists then transferred the gut bacteria from their study participants to mice that were bred to be germ-free. Because they were bred not to have any of their own gut bacteria, scientists could later introduce bacteria and watch what happened as they started growing.
The mice that got the bacteria from the humans on the high-fiber diets had better fasting blood sugar levels than mice that got bacteria from people on the usual diabetes diet, even though they were eating the same chow.
The study was published in the journal Science.
Getting More Daily Fiber
The study authors say it would be difficult for the average person to copy their high-fiber diet. People in the high-fiber part of the study ate a specially prepared gruel made from oats, white beans, yellow corn, red beans, yams, peanuts, and lotus seeds, along with two whole grains that are unfamiliar to Westerners -- green buckwheat and adlay, or Job’s tears. They also got more fiber in the form of powders that included bitter melon, kudzu starch, inulin, and resistant dextrin...
https://www.webmd.com/diabetes/news/20180309/enlisting-gut-bacteria-and-fiber-to...
________________________________________________________
Rutgers University. "Fiber-fermenting bacteria improve health of type 2 diabetes patients: Dietary fibers promote gut bacteria that benefit blood glucose control." ScienceDaily. ScienceDaily, 8 March 2018.
________________________________________________________
Liping Zhao, Feng Zhang, Xiaoying Ding, Guojun Wu, Yan Y. Lam, Xuejiao Wang, Huaqing Fu, Xinhe Xue, Chunhua Lu, Jilin Ma, Lihua Yu, Chengmei Xu, Zhongying Ren, Ying Xu, Songmei Xu, Hongli Shen, Xiuli Zhu, Yu Shi, Qingyun Shen, Weiping Dong, Rui Liu, Yunxia Ling, Yue Zeng, Xingpeng Wang, Qianpeng Zhang, Jing Wang, Linghua Wang, Yanqiu Wu, Benhua Zeng, Hong Wei, Menghui Zhang, Yongde Peng, Chenhong Zhang. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 2018; 359 (6380): 1151 DOI: 10.1126/science.aao5774
http://science.sciencemag.org/content/359/6380/1151
________________________________________________________
22pmackey
>21 margd: Thanks, I really appreciate your taking the time to write all this. Funny you mention fiber. You're the second person this year. A friend of mine is a retired Home Economics (I don't know the right term anymore) teacher who told me the same thing: Focus on fiber. I've been focused on counting carbs (increasing good carbs, cutting out bad). A month ago, my doctor put me on Trulicity which slows down digestion. That has helped smooth out the sugar highs and lows -- the carb cravings were hard to deal with.
23margd
We evolved during periods of starvation. No surprise that body has so many ways to have us eat, even in plenty. Here's yet another one:
S.X. Luo et al. Regulation of feeding by somatostatin neurons in the tuberal nucleus. Science. Vol. 361, July 6, 2018, p. 76. doi:10.1126/science.aar4983. http://science.sciencemag.org/content/361/6397/76
___________________________________________________________
Nerve cells that help control hunger have been ID’d in mice
Targeting similar cells in people could mark a new way to regulate appetites
Laura Sanders | July 5, 2018
Newly identified nerve cells deep in the brains of mice compel them to eat. Similar cells exist in people, too, and may ultimately represent a new way to target eating disorders and obesity.
...Certain nerve cells in the human brain region called the nucleus tuberalis lateralis, or NTL, are known to malfunction in neurodegenerative diseases such as Huntington’s and Alzheimer’s.
...In people, the NTL is a small bump along the bottom edge of the hypothalamus, a brain structure known to regulate eating behavior. But in mice, a similar structure wasn’t thought to exist at all, until Fu and colleagues discovered it by chance.
...The neurons sprang into action when the mice were hungry, or when the hunger-signaling hormone ghrelin was around, the team found. And when the researchers artificially activated the cells, using either laser light or molecular techniques, the mice ate more and gained weight faster than normal mice. Conversely, when the researchers killed the neurons, the mice didn’t eat as much and gained less weight than mice that still possessed the cells. The results suggest that, in mice, these neurons influence the impulse to eat — and subsequent changes in weight.
...Both Alzheimer’s and Huntington’s have been tied to metabolic problems and changes in appetite. The demise of appetite-controlling cells in the NTL might help explain why.
If NTL cells do control appetite in humans, that brain region wouldn’t be working alone. Far from it. Neighboring nerve cells in and around the hypothalamus are also known to play big roles in prodding the body to eat when food is available
...Tweaking the behavior of these appetite-controlling cells, perhaps with drugs, may one day offer a way to treat obesity or eating disorders such as anorexia.
https://www.sciencenews.org/article/nerve-cells-help-control-hunger-have-been-id...
S.X. Luo et al. Regulation of feeding by somatostatin neurons in the tuberal nucleus. Science. Vol. 361, July 6, 2018, p. 76. doi:10.1126/science.aar4983. http://science.sciencemag.org/content/361/6397/76
___________________________________________________________
Nerve cells that help control hunger have been ID’d in mice
Targeting similar cells in people could mark a new way to regulate appetites
Laura Sanders | July 5, 2018
Newly identified nerve cells deep in the brains of mice compel them to eat. Similar cells exist in people, too, and may ultimately represent a new way to target eating disorders and obesity.
...Certain nerve cells in the human brain region called the nucleus tuberalis lateralis, or NTL, are known to malfunction in neurodegenerative diseases such as Huntington’s and Alzheimer’s.
...In people, the NTL is a small bump along the bottom edge of the hypothalamus, a brain structure known to regulate eating behavior. But in mice, a similar structure wasn’t thought to exist at all, until Fu and colleagues discovered it by chance.
...The neurons sprang into action when the mice were hungry, or when the hunger-signaling hormone ghrelin was around, the team found. And when the researchers artificially activated the cells, using either laser light or molecular techniques, the mice ate more and gained weight faster than normal mice. Conversely, when the researchers killed the neurons, the mice didn’t eat as much and gained less weight than mice that still possessed the cells. The results suggest that, in mice, these neurons influence the impulse to eat — and subsequent changes in weight.
...Both Alzheimer’s and Huntington’s have been tied to metabolic problems and changes in appetite. The demise of appetite-controlling cells in the NTL might help explain why.
If NTL cells do control appetite in humans, that brain region wouldn’t be working alone. Far from it. Neighboring nerve cells in and around the hypothalamus are also known to play big roles in prodding the body to eat when food is available
...Tweaking the behavior of these appetite-controlling cells, perhaps with drugs, may one day offer a way to treat obesity or eating disorders such as anorexia.
https://www.sciencenews.org/article/nerve-cells-help-control-hunger-have-been-id...
24margd
Early gene mutation, which may have led to rise of genus Homo, is a mixed blessing--increases risk of Type 2 diabetes.
A single gene mutation may have helped humans become optimal long-distance runners
September 11, 2018, University of California - San Diego
...lost gene may also have contributed to humanity's well-documented claim to be among the best long-distance runners in the animal kingdom.
...might have contributed to the origin of Homo, the genus that includes modern Homo sapiens and extinct species like Homo habilis and Homo erectus.
...contributed to improved skeletal muscle capacity for oxygen utilization...
...enhanced innate immunity in early hominids...
...certain sialic acids are associated with increased risk of type 2 diabetes; may contribute to elevated cancer risk associated with red meat consumption; and trigger inflammation.
"They are a double-edged sword," said Varki. "The consequence of a single lost gene and a small molecular change that appears to have profoundly altered human biology and abilities going back to our origins."...
https://phys.org/news/2018-09-gene-mutation-humans-optimal-long-distance.html
More information: Human-like Cmah Inactivation in Mice Increases Running Endurance and Decreases Muscle Fatigability: Implications for Human Evolution, Proceedings of the Royal Society B, rspb.royalsocietypublishing.or … .1098/rspb.2018.1656
________________________________________________________________
Missing molecule raises diabetes risk in humans
March 2, 2011, University of California - San Diego
https://medicalxpress.com/news/2011-03-molecule-diabetes-humans.html
A single gene mutation may have helped humans become optimal long-distance runners
September 11, 2018, University of California - San Diego
...lost gene may also have contributed to humanity's well-documented claim to be among the best long-distance runners in the animal kingdom.
...might have contributed to the origin of Homo, the genus that includes modern Homo sapiens and extinct species like Homo habilis and Homo erectus.
...contributed to improved skeletal muscle capacity for oxygen utilization...
...enhanced innate immunity in early hominids...
...certain sialic acids are associated with increased risk of type 2 diabetes; may contribute to elevated cancer risk associated with red meat consumption; and trigger inflammation.
"They are a double-edged sword," said Varki. "The consequence of a single lost gene and a small molecular change that appears to have profoundly altered human biology and abilities going back to our origins."...
https://phys.org/news/2018-09-gene-mutation-humans-optimal-long-distance.html
More information: Human-like Cmah Inactivation in Mice Increases Running Endurance and Decreases Muscle Fatigability: Implications for Human Evolution, Proceedings of the Royal Society B, rspb.royalsocietypublishing.or … .1098/rspb.2018.1656
________________________________________________________________
Missing molecule raises diabetes risk in humans
March 2, 2011, University of California - San Diego
https://medicalxpress.com/news/2011-03-molecule-diabetes-humans.html
25margd
I didn't see mechanism by which household disinfectants might be affecting children's gut biota and weight, e.g.,
1. did disinfectant reduce microbes available TO baby,
2. kill some species microbes IN baby,
3. eco-friendly products are just marker for healthier diet & habits in the home, or
4. ____?
I suspect # 1 and 3?
__________________________________________________________________________
Household disinfectants could be making kids overweight by altering their gut microbiota (1:00)
CMAJ | Sep 17, 2018
Research published in the Canadian Medical Association Journal has found that household cleaning products may contribute to kids' overweight by altering their gut microbiota.
https://www.youtube.com/watch?v=2OUXHwkpc28
___________________________________________________________________________
Household cleaning products may contribute to kids' overweight by altering their gut microbiota
September 17, 2018, Canadian Medical Association Journal
...analyzed the gut flora of 757 infants from the general population at age 3-4 months and weight at ages 1 and 3 years, looking at exposure to disinfectants, detergents and eco-friendly products used in the home.
...Associations with altered gut flora in babies 3-4 months old were strongest for frequent use of household disinfectants such as multisurface cleaners, which showed lower levels of Haemophilus and Clostridium bacteria but higher levels of Lachnospiraceae. The researchers also observed an increase in Lachnospiraceae bacteria with more frequent cleaning with disinfectants. They did not find the same association with detergents or eco-friendly cleaners. Studies of piglets have found similar changes in the gut microbiome when exposed to aerosol disinfectants.
"...when they were 3 years old, their body mass index was higher than children not exposed to heavy home use of disinfectants as an infant"...
Babies living in households that used eco-friendly cleaners had different microbiota and were less likely to be overweight as toddlers.
"Those infants growing up in households with heavy use of eco cleaners had much lower levels of the gut microbes Enterobacteriaceae. However, we found no evidence that these gut microbiome changes caused the reduced obesity risk," she said.
She suggests that the use of eco-friendly products may be linked to healthier overall maternal lifestyles and eating habits, contributing in turn to the healthier gut microbiomes and weight of their infants...
https://medicalxpress.com/news/2018-09-household-products-contribute-kids-overwe...
___________________________________________________________________________
Mon H. Tun et al. Postnatal exposure to household disinfectants, infant gut microbiota and subsequent risk of overweight in children, Canadian Medical Association Journal (2018). DOI: 10.1503/cmaj.170809
Conclusion
Antibacterial cleaning products have the capacity to change the environmental microbiome and alter risk for child overweight. Our study provides novel information regarding the impact of these products on infant gut microbial composition and outcomes of overweight in the same population. We found Lachnospiraceae to be enriched in infant gut microbiota with frequent postnatal use of domestic disinfectants but not eco-friendly products; genus Clostridium and Haemophilus were reduced concurrently. Evidence of statistical mediation with Lachnospiraceae abundance showed a role for this disinfectant-related change to gut microbiota in causing overweight. We did not observe mediation for infant fecal Enterobacteriaceae, suggesting an alternate pathway for the association between postnatal eco-friendly product use and reduced child overweight. Further study is required on the mechanisms through which household cleaning products alter gut microbial composition and the subsequent role this might have on metabolic disease...
Questionnaire: http://www.cmaj.ca/content/cmaj/suppl/2018/09/13/190.37.E1097.DC1/170809-res-1-a...
Use frequency: daily weekly monthly less than monthly not used
Disinfectants
1 Multisurface cleaner
2 Toilet Bowl Cleaner
3 Purell type cleaner
4 Floor cleaner
5 Bleach
6 Disinfectant in home in general
7 Disinfectant in Bedroom
8 Bathroom tile cleaner...
Detergent... (8)
Other chemicals/cleaning products... (14)
You may also like
The association between ownership of common household devices and obesity and diabetes in high, middle and low income countries
Scott A. Lear, CMAJ
Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months
Meghan B. Azad, CMAJ
Effects of low income on infant health
Louise Séguin, CMAJ
How delivery mode and feeding can shape the bacterial community in the infant gut
Se Jin Song, CMAJ
Prevalence of and risk factors for childhood overweight and obesity
Paul J. Veugelers et al., CMAJ
Household cleaning products may contribute to kids' overweight by altering their gut microbiota
MedicalXpress
Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring
Hein M. Tun et al., JAMA Pediatr
Gut Microbiota May Affect Vertical Transmission of Being Overweight
PracticeUpdate
Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life
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PracticeUpdate
_________________________________________________________________________________
Moira K. Differding et al. Are household disinfectants microbially mediated obesogens?, Canadian Medical Association Journal (2018). DOI: 10.1503/cmaj.181134
1. did disinfectant reduce microbes available TO baby,
2. kill some species microbes IN baby,
3. eco-friendly products are just marker for healthier diet & habits in the home, or
4. ____?
I suspect # 1 and 3?
__________________________________________________________________________
Household disinfectants could be making kids overweight by altering their gut microbiota (1:00)
CMAJ | Sep 17, 2018
Research published in the Canadian Medical Association Journal has found that household cleaning products may contribute to kids' overweight by altering their gut microbiota.
https://www.youtube.com/watch?v=2OUXHwkpc28
___________________________________________________________________________
Household cleaning products may contribute to kids' overweight by altering their gut microbiota
September 17, 2018, Canadian Medical Association Journal
...analyzed the gut flora of 757 infants from the general population at age 3-4 months and weight at ages 1 and 3 years, looking at exposure to disinfectants, detergents and eco-friendly products used in the home.
...Associations with altered gut flora in babies 3-4 months old were strongest for frequent use of household disinfectants such as multisurface cleaners, which showed lower levels of Haemophilus and Clostridium bacteria but higher levels of Lachnospiraceae. The researchers also observed an increase in Lachnospiraceae bacteria with more frequent cleaning with disinfectants. They did not find the same association with detergents or eco-friendly cleaners. Studies of piglets have found similar changes in the gut microbiome when exposed to aerosol disinfectants.
"...when they were 3 years old, their body mass index was higher than children not exposed to heavy home use of disinfectants as an infant"...
Babies living in households that used eco-friendly cleaners had different microbiota and were less likely to be overweight as toddlers.
"Those infants growing up in households with heavy use of eco cleaners had much lower levels of the gut microbes Enterobacteriaceae. However, we found no evidence that these gut microbiome changes caused the reduced obesity risk," she said.
She suggests that the use of eco-friendly products may be linked to healthier overall maternal lifestyles and eating habits, contributing in turn to the healthier gut microbiomes and weight of their infants...
https://medicalxpress.com/news/2018-09-household-products-contribute-kids-overwe...
___________________________________________________________________________
Mon H. Tun et al. Postnatal exposure to household disinfectants, infant gut microbiota and subsequent risk of overweight in children, Canadian Medical Association Journal (2018). DOI: 10.1503/cmaj.170809
Conclusion
Antibacterial cleaning products have the capacity to change the environmental microbiome and alter risk for child overweight. Our study provides novel information regarding the impact of these products on infant gut microbial composition and outcomes of overweight in the same population. We found Lachnospiraceae to be enriched in infant gut microbiota with frequent postnatal use of domestic disinfectants but not eco-friendly products; genus Clostridium and Haemophilus were reduced concurrently. Evidence of statistical mediation with Lachnospiraceae abundance showed a role for this disinfectant-related change to gut microbiota in causing overweight. We did not observe mediation for infant fecal Enterobacteriaceae, suggesting an alternate pathway for the association between postnatal eco-friendly product use and reduced child overweight. Further study is required on the mechanisms through which household cleaning products alter gut microbial composition and the subsequent role this might have on metabolic disease...
Questionnaire: http://www.cmaj.ca/content/cmaj/suppl/2018/09/13/190.37.E1097.DC1/170809-res-1-a...
Use frequency: daily weekly monthly less than monthly not used
Disinfectants
1 Multisurface cleaner
2 Toilet Bowl Cleaner
3 Purell type cleaner
4 Floor cleaner
5 Bleach
6 Disinfectant in home in general
7 Disinfectant in Bedroom
8 Bathroom tile cleaner...
Detergent... (8)
Other chemicals/cleaning products... (14)
You may also like
The association between ownership of common household devices and obesity and diabetes in high, middle and low income countries
Scott A. Lear, CMAJ
Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months
Meghan B. Azad, CMAJ
Effects of low income on infant health
Louise Séguin, CMAJ
How delivery mode and feeding can shape the bacterial community in the infant gut
Se Jin Song, CMAJ
Prevalence of and risk factors for childhood overweight and obesity
Paul J. Veugelers et al., CMAJ
Household cleaning products may contribute to kids' overweight by altering their gut microbiota
MedicalXpress
Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring
Hein M. Tun et al., JAMA Pediatr
Gut Microbiota May Affect Vertical Transmission of Being Overweight
PracticeUpdate
Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life
Malcolm R. Sears et al., JAMA Pediatr
Association of Obesity With Feeding Practices in Infancy
PracticeUpdate
_________________________________________________________________________________
Moira K. Differding et al. Are household disinfectants microbially mediated obesogens?, Canadian Medical Association Journal (2018). DOI: 10.1503/cmaj.181134
26margd
Activity by the choline-cutting microbes could play a role in obesity and may diminish availability of the nutrient to mom and fetus during pregnancy:
K.A. Romano et al. Metabolic, epigenetic, and transgenerational effects of gut bacterial choline consumption. Cell Host & Microbe. Vol. 22, September 13, 2017, p. 279. doi:10.1016/j.chom.2017.07.021. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30304-9
Highlights
Gut bacteria compete with the host for choline, decreasing bioavailability
Microbial choline degradation depletes methyl-donor metabolites
Microbial choline utilization alters in utero epigenetic programming of the brain
Mice with choline-consuming gut microbiota display altered behavior
Summary
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.
K.A. Romano et al. Metabolic, epigenetic, and transgenerational effects of gut bacterial choline consumption. Cell Host & Microbe. Vol. 22, September 13, 2017, p. 279. doi:10.1016/j.chom.2017.07.021. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30304-9
Highlights
Gut bacteria compete with the host for choline, decreasing bioavailability
Microbial choline degradation depletes methyl-donor metabolites
Microbial choline utilization alters in utero epigenetic programming of the brain
Mice with choline-consuming gut microbiota display altered behavior
Summary
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.
27margd
How Dad’s Stresses Get Passed Along to Offspring
Esther Landhuis on November 8, 2018
Mouse studies show tiny intercellular pods convey to sperm a legacy of a father’s hard knocks in life
A stressed-out and traumatized father can leave scars in his children. New research suggests this happens because sperm “learn” paternal experiences via a mysterious mode of intercellular communication in which small blebs break off one cell and fuse with another.
Carrying proteins, lipids and nucleic acids, these particles ejected from a cell act like a postal system that extends to all parts of the body, releasing little packages known as extracellular vesicles. Their contents seem carefully chosen. “The cargo inside the vesicle determines not just where it came from but where it’s going and what it’s doing when it gets there,” says Tracy Bale, a neurobiologist at the University of Maryland School of Medicine.
Preliminary research Bale and others, announced this week at the annual meeting of the Society for Neuroscience in San Diego, shows how extracellular vesicles can regulate brain circuits and help diagnose neurodegenerative diseases—in addition to altering sperm to disrupt the brain health of resulting offspring.
Striking evidence that harsh conditions affect a man’s children came from crop failures and war ravaging Europe more than a century ago. In those unplanned human experiments, prolonged famine appeared to set off a host of health changes in future generations, including higher cholesterol levels and increased rates of obesity and diabetes....
https://www.scientificamerican.com/article/how-dads-stresses-get-passed-along-to...
Esther Landhuis on November 8, 2018
Mouse studies show tiny intercellular pods convey to sperm a legacy of a father’s hard knocks in life
A stressed-out and traumatized father can leave scars in his children. New research suggests this happens because sperm “learn” paternal experiences via a mysterious mode of intercellular communication in which small blebs break off one cell and fuse with another.
Carrying proteins, lipids and nucleic acids, these particles ejected from a cell act like a postal system that extends to all parts of the body, releasing little packages known as extracellular vesicles. Their contents seem carefully chosen. “The cargo inside the vesicle determines not just where it came from but where it’s going and what it’s doing when it gets there,” says Tracy Bale, a neurobiologist at the University of Maryland School of Medicine.
Preliminary research Bale and others, announced this week at the annual meeting of the Society for Neuroscience in San Diego, shows how extracellular vesicles can regulate brain circuits and help diagnose neurodegenerative diseases—in addition to altering sperm to disrupt the brain health of resulting offspring.
Striking evidence that harsh conditions affect a man’s children came from crop failures and war ravaging Europe more than a century ago. In those unplanned human experiments, prolonged famine appeared to set off a host of health changes in future generations, including higher cholesterol levels and increased rates of obesity and diabetes....
https://www.scientificamerican.com/article/how-dads-stresses-get-passed-along-to...
28margd
"OUR OBSERVATIONS CHALLENGE THE BELIEF THAT ALL CALORIES ARE THE SAME TO THE BODY"
________________________________________________________________
Cara B Ebbeling et al. 2018. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4583 (Published 14 November 2018)
Abstract
Interventions. After 12% weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%; moderate, 40%; or low, 20%) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).
Results. Total energy expenditure differed by diet in the intention-to-treat analysis, with a linear trend of 52 kcal/d for every 10% decrease in the contribution of carbohydrate to total energy intake. Change in total energy expenditure was 91 kcal/d greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis, the respective differences were 131 kcal/d and 278 kcal/d. Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).
Conclusions Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.
_____________________________________________________________
Low-carb diets cause people to burn more calories
Children's Hospital Boston | November 14, 2018,
Most people regain the weight they lose from dieting within one or two years, in part because the body adapts by slowing metabolism and burning fewer calories. A meticulous study led by Boston Children's Hospital, in partnership with Framingham State University, now finds that eating fewer carbohydrates increases the number of calories burned. The findings, published November 14 in the BMJ, suggest that low-carb diets can help people maintain weight loss, making obesity treatment more effective.
...Over the 20 weeks, total energy expenditure was significantly greater on the low-carbohydrate diet versus the high-carbohydrate diet. At the same average body weight, participants who consumed the low-carb diet burned about 250 kilocalories a day more than those on the high-carb diet.
"If this difference persists—and we saw no drop-off during the 20 weeks of our study—the effect would translate into about a 20-pound weight loss after three years, with no change in calorie intake," says Ebbeling.
In people with the highest insulin secretion at baseline, the difference in calorie expenditure between the low- and high-carb diets was even greater, about 400 kilocalories per day, consistent with what the Carbohydrate-Insulin Model would predict. Ghrelin, a hormone thought to reduce calorie burning, was significantly lower on the low- versus high-carb diet.
"Our observations challenge the belief that all calories are the same to the body," says Ebbeling. "Our study did not measure hunger and satiety, but other studies suggest that low-carb diets also decrease hunger, which could help with weight loss in the long term."...
https://medicalxpress.com/news/2018-11-low-carb-diets-people-calories.html
________________________________________________________________
Cara B Ebbeling et al. 2018. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4583 (Published 14 November 2018)
Abstract
Interventions. After 12% weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%; moderate, 40%; or low, 20%) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).
Results. Total energy expenditure differed by diet in the intention-to-treat analysis, with a linear trend of 52 kcal/d for every 10% decrease in the contribution of carbohydrate to total energy intake. Change in total energy expenditure was 91 kcal/d greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis, the respective differences were 131 kcal/d and 278 kcal/d. Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).
Conclusions Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.
_____________________________________________________________
Low-carb diets cause people to burn more calories
Children's Hospital Boston | November 14, 2018,
Most people regain the weight they lose from dieting within one or two years, in part because the body adapts by slowing metabolism and burning fewer calories. A meticulous study led by Boston Children's Hospital, in partnership with Framingham State University, now finds that eating fewer carbohydrates increases the number of calories burned. The findings, published November 14 in the BMJ, suggest that low-carb diets can help people maintain weight loss, making obesity treatment more effective.
...Over the 20 weeks, total energy expenditure was significantly greater on the low-carbohydrate diet versus the high-carbohydrate diet. At the same average body weight, participants who consumed the low-carb diet burned about 250 kilocalories a day more than those on the high-carb diet.
"If this difference persists—and we saw no drop-off during the 20 weeks of our study—the effect would translate into about a 20-pound weight loss after three years, with no change in calorie intake," says Ebbeling.
In people with the highest insulin secretion at baseline, the difference in calorie expenditure between the low- and high-carb diets was even greater, about 400 kilocalories per day, consistent with what the Carbohydrate-Insulin Model would predict. Ghrelin, a hormone thought to reduce calorie burning, was significantly lower on the low- versus high-carb diet.
"Our observations challenge the belief that all calories are the same to the body," says Ebbeling. "Our study did not measure hunger and satiety, but other studies suggest that low-carb diets also decrease hunger, which could help with weight loss in the long term."...
https://medicalxpress.com/news/2018-11-low-carb-diets-people-calories.html
29margd
...Snack on Brazil Nuts
We’ve known noshing on nuts instead of empty calories is healthy, but now researchers have zeroed in on what may be the best nut for keeping off extra pounds — Brazil nuts. Their slimming secret comes from their especially high content of the mineral selenium, which is used to make a hormone that regulates body weight; low levels of the mineral have been reported in obese people, says Mee Young Hong, a professor in the School of Exercise and Nutritional Sciences at San Diego State University. While the average nut has anywhere from 3 to 5 micrograms of selenium per ounce, Brazil nuts have a whopping 544 micrograms.
Hong’s study, released today, compared the impact pretzels versus Brazil nuts had on blood sugar in a small group of healthy adults. He found that while pretzels caused blood sugar to spike, Brazil nuts helped to stabilize levels. Moreover, after eating Brazil nuts, people reported feeling fuller longer. In general, nuts are a good source of protein, fiber and healthy fats — and “all of these nutrients take longer to process and absorb, so the sensation of satiety lasts for a longer period,” Hong explains.
Brazil nuts aren’t your favorite? A tandem study, also released today, shows that eating 1 ounce daily of any nut — even peanuts — can help you stave off the one pound most adults gain each year. That’s what researchers at Harvard’s School of Public Health found in a study that analyzed data from records of more than 125,000 adults. Having nuts in your diet, researchers found, also helped people keep the weight off over a four-year period. Nuts were particularly helpful when eaten in place of red meat, french fries, chips or desserts, says Xiaoran Liu, lead author of the study and a research associate in the nutrition department of Harvard School of Public Health in Boston...
https://www.aarp.org/health/healthy-living/info-2018/heart-healthy-eating-aha.ht...
Also:
American Heart Association. "Nuts for nuts? Daily serving may help control weight and benefit health."
ScienceDaily, 5 November 2018.
www.sciencedaily.com/releases/2018/11/181105081742.htm
We’ve known noshing on nuts instead of empty calories is healthy, but now researchers have zeroed in on what may be the best nut for keeping off extra pounds — Brazil nuts. Their slimming secret comes from their especially high content of the mineral selenium, which is used to make a hormone that regulates body weight; low levels of the mineral have been reported in obese people, says Mee Young Hong, a professor in the School of Exercise and Nutritional Sciences at San Diego State University. While the average nut has anywhere from 3 to 5 micrograms of selenium per ounce, Brazil nuts have a whopping 544 micrograms.
Hong’s study, released today, compared the impact pretzels versus Brazil nuts had on blood sugar in a small group of healthy adults. He found that while pretzels caused blood sugar to spike, Brazil nuts helped to stabilize levels. Moreover, after eating Brazil nuts, people reported feeling fuller longer. In general, nuts are a good source of protein, fiber and healthy fats — and “all of these nutrients take longer to process and absorb, so the sensation of satiety lasts for a longer period,” Hong explains.
Brazil nuts aren’t your favorite? A tandem study, also released today, shows that eating 1 ounce daily of any nut — even peanuts — can help you stave off the one pound most adults gain each year. That’s what researchers at Harvard’s School of Public Health found in a study that analyzed data from records of more than 125,000 adults. Having nuts in your diet, researchers found, also helped people keep the weight off over a four-year period. Nuts were particularly helpful when eaten in place of red meat, french fries, chips or desserts, says Xiaoran Liu, lead author of the study and a research associate in the nutrition department of Harvard School of Public Health in Boston...
https://www.aarp.org/health/healthy-living/info-2018/heart-healthy-eating-aha.ht...
Also:
American Heart Association. "Nuts for nuts? Daily serving may help control weight and benefit health."
ScienceDaily, 5 November 2018.
www.sciencedaily.com/releases/2018/11/181105081742.htm
302wonderY
>29 margd: Aha! Christmas gifting idea help.
31margd
Brazil nuts almost sound too good to be true:
One study, at least, found that a single serving of Brazil nuts may bring cholesterol levels down faster than statin drugs and keep them down even a month after that single ingestion. (I used to keep a stash in the freezer, and grab one when I visited. Should restock.)
They grow best in pristine forests, so a resource for local people.
_____________________________________________________________
Four Nuts Once a Month
Michael Greger M.D. FACLM September 15th, 2014 Volume 20
A single serving of Brazil nuts may bring cholesterol levels down faster than statin drugs and keep them down even a month after that single ingestion.
https://nutritionfacts.org/video/four-nuts-once-a-month/
_____________________________________________________________
The Brazil nut family is in the order Ericales, as are other well-known plants such as blueberries, cranberries, sapote, gutta-percha, tea, phlox and persimmons.
The Brazil nut tree is...native to the Guianas, Venezuela, Brazil, eastern Colombia, eastern Peru, and eastern Bolivia. It occurs as scattered trees in large forests on the banks of the Amazon River, Rio Negro, Tapajós, and the Orinoco.
...The Brazil nut is a large tree, reaching 50 m (160 ft) tall and with a trunk 1 to 2 m (3.3 to 6.6 ft) in diameter, making it among the largest of trees in the Amazon rainforests. It may live for 500 years or more, and according to some authorities often reaches an age of 1,000 years.
...Brazil nut trees produce fruit almost exclusively in pristine forests, as disturbed forests lack the large-bodied bees of the genera Bombus, Centris, Epicharis, Eulaema, and Xylocopa which are the only ones capable of pollinating the tree's flowers, with different bee genera being the primary pollinators in different areas, and different times of year. Brazil nuts have been harvested from plantations, but production is low and is currently not economically viable.
...Brazil nuts for international trade can come from wild collection rather than from plantations. This has been advanced as a model for generating income from a tropical forest without destroying it. The nuts are gathered by migrant workers known as castanheiros.
Analysis of tree ages in areas that are harvested show that moderate and intense gathering takes so many seeds that not enough are left to replace older trees as they die. Sites with light gathering activities had many young trees, while sites with intense gathering practices had hardly any young trees.
https://en.wikipedia.org/wiki/Brazil_nut
One study, at least, found that a single serving of Brazil nuts may bring cholesterol levels down faster than statin drugs and keep them down even a month after that single ingestion. (I used to keep a stash in the freezer, and grab one when I visited. Should restock.)
They grow best in pristine forests, so a resource for local people.
_____________________________________________________________
Four Nuts Once a Month
Michael Greger M.D. FACLM September 15th, 2014 Volume 20
A single serving of Brazil nuts may bring cholesterol levels down faster than statin drugs and keep them down even a month after that single ingestion.
https://nutritionfacts.org/video/four-nuts-once-a-month/
_____________________________________________________________
The Brazil nut family is in the order Ericales, as are other well-known plants such as blueberries, cranberries, sapote, gutta-percha, tea, phlox and persimmons.
The Brazil nut tree is...native to the Guianas, Venezuela, Brazil, eastern Colombia, eastern Peru, and eastern Bolivia. It occurs as scattered trees in large forests on the banks of the Amazon River, Rio Negro, Tapajós, and the Orinoco.
...The Brazil nut is a large tree, reaching 50 m (160 ft) tall and with a trunk 1 to 2 m (3.3 to 6.6 ft) in diameter, making it among the largest of trees in the Amazon rainforests. It may live for 500 years or more, and according to some authorities often reaches an age of 1,000 years.
...Brazil nut trees produce fruit almost exclusively in pristine forests, as disturbed forests lack the large-bodied bees of the genera Bombus, Centris, Epicharis, Eulaema, and Xylocopa which are the only ones capable of pollinating the tree's flowers, with different bee genera being the primary pollinators in different areas, and different times of year. Brazil nuts have been harvested from plantations, but production is low and is currently not economically viable.
...Brazil nuts for international trade can come from wild collection rather than from plantations. This has been advanced as a model for generating income from a tropical forest without destroying it. The nuts are gathered by migrant workers known as castanheiros.
Analysis of tree ages in areas that are harvested show that moderate and intense gathering takes so many seeds that not enough are left to replace older trees as they die. Sites with light gathering activities had many young trees, while sites with intense gathering practices had hardly any young trees.
https://en.wikipedia.org/wiki/Brazil_nut
32mamzel
> Funny, I used to think that Brazil nuts were just fillers in the can of mixed nuts. I thought they were quite greasy. I'll have to rethink that now.
33margd
An essay on one man's journey: he's Chris-Christie-sized, I think, and it hasn't been easy.
The Weight I Carry
Tommy Tomlinson | Jan 9, 2019
What it’s like to be too big in America
https://www.theatlantic.com/health/archive/2019/01/weight-loss-essay-tomlinson/5...
The Weight I Carry
Tommy Tomlinson | Jan 9, 2019
What it’s like to be too big in America
https://www.theatlantic.com/health/archive/2019/01/weight-loss-essay-tomlinson/5...
34margd
Study* reveals how much fiber we should eat to prevent disease
Ana Sandoiu | jan 11, 2019
...Overall, the research found that people who consume the most fiber in their diet are 15–30 percent less likely to die prematurely from any cause or a cardiovascular condition, compared with those who eat the least fiber.
Consuming foods rich in fiber correlated with a 16–24 percent lower incidence of coronary heart disease, stroke, type 2 diabetes, and colon cancer.
Fiber-rich foods include whole grains, vegetables, fruit, and pulses, such as peas, beans, lentils, and chickpeas.
The analysis also revealed that the amount of fiber that people should consume daily to gain these health benefits is 25–29 grams (g). By comparison, adults in the United States consume 15 g of fiber daily, on average.
The authors also suggest that consuming more than 29 g of fiber per day may yield even more health benefits.
However, they do caution that, while the study in itself did not find any adverse health effects of consuming fiber, eating too much of it may be damaging for people with insufficient iron or minerals.
Eating large amounts of whole grains can further deplete the body of iron, explain the researchers.
Finally, the clinical trials included in the study also revealed that consuming more fiber correlates strongly with lower weight and lower cholesterol levels...
https://www.medicalnewstoday.com/articles/324153.php
______________________________________________________
*Andrew Reynolds et al. 2019. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. The Lancet.
January 10, 2019 DOI:https://doi.org/10.1016/S0140-6736(18)31809-9 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31809-9/fullt...
Summary
Background
Previous systematic reviews and meta-analyses explaining the relationship between carbohydrate quality and health have usually examined a single marker and a limited number of clinical outcomes. We aimed to more precisely quantify the predictive potential of several markers, to determine which markers are most useful, and to establish an evidence base for quantitative recommendations for intakes of dietary fibre.
Methods
We did a series of systematic reviews and meta-analyses of prospective studies published from database inception to April 30, 2017, and randomised controlled trials published from database inception to Feb 28, 2018, which reported on indicators of carbohydrate quality and non-communicable disease incidence, mortality, and risk factors. Studies were identified by searches in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We excluded prospective studies and trials reporting on participants with a chronic disease, and weight loss trials or trials involving supplements. Searches, data extraction, and bias assessment were duplicated independently. Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, dose-response testing, and subgroup analyses. The GRADE approach was used to assess quality of evidence.
Findings
Just under 135 million person-years of data from 185 prospective studies and 58 clinical trials with 4635 adult participants were included in the analyses. Observational data suggest a 15–30% decrease in all-cause and cardiovascular related mortality, and incidence of coronary heart disease, stroke incidence and mortality, type 2 diabetes, and colorectal cancer when comparing the highest dietary fibre consumers with the lowest consumers Clinical trials show significantly lower bodyweight, systolic blood pressure, and total cholesterol when comparing higher with lower intakes of dietary fibre. Risk reduction associated with a range of critical outcomes was greatest when daily intake of dietary fibre was between 25 g and 29 g. Dose-response curves suggested that higher intakes of dietary fibre could confer even greater benefit to protect against cardiovascular diseases, type 2 diabetes, and colorectal and breast cancer. Similar findings for whole grain intake were observed. Smaller or no risk reductions were found with the observational data when comparing the effects of diets characterised by low rather than higher glycaemic index or load. The certainty of evidence for relationships between carbohydrate quality and critical outcomes was graded as moderate for dietary fibre, low to moderate for whole grains, and low to very low for dietary glycaemic index and glycaemic load. Data relating to other dietary exposures are scarce.
Interpretation
Findings from prospective studies and clinical trials associated with relatively high intakes of dietary fibre and whole grains were complementary, and striking dose-response evidence indicates that the relationships to several non-communicable diseases could be causal. Implementation of recommendations to increase dietary fibre intake and to replace refined grains with whole grains is expected to benefit human health. A major strength of the study was the ability to examine key indicators of carbohydrate quality in relation to a range of non-communicable disease outcomes from cohort studies and randomised trials in a single study. Our findings are limited to risk reduction in the population at large rather than those with chronic disease.
Ana Sandoiu | jan 11, 2019
...Overall, the research found that people who consume the most fiber in their diet are 15–30 percent less likely to die prematurely from any cause or a cardiovascular condition, compared with those who eat the least fiber.
Consuming foods rich in fiber correlated with a 16–24 percent lower incidence of coronary heart disease, stroke, type 2 diabetes, and colon cancer.
Fiber-rich foods include whole grains, vegetables, fruit, and pulses, such as peas, beans, lentils, and chickpeas.
The analysis also revealed that the amount of fiber that people should consume daily to gain these health benefits is 25–29 grams (g). By comparison, adults in the United States consume 15 g of fiber daily, on average.
The authors also suggest that consuming more than 29 g of fiber per day may yield even more health benefits.
However, they do caution that, while the study in itself did not find any adverse health effects of consuming fiber, eating too much of it may be damaging for people with insufficient iron or minerals.
Eating large amounts of whole grains can further deplete the body of iron, explain the researchers.
Finally, the clinical trials included in the study also revealed that consuming more fiber correlates strongly with lower weight and lower cholesterol levels...
https://www.medicalnewstoday.com/articles/324153.php
______________________________________________________
*Andrew Reynolds et al. 2019. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. The Lancet.
January 10, 2019 DOI:https://doi.org/10.1016/S0140-6736(18)31809-9 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31809-9/fullt...
Summary
Background
Previous systematic reviews and meta-analyses explaining the relationship between carbohydrate quality and health have usually examined a single marker and a limited number of clinical outcomes. We aimed to more precisely quantify the predictive potential of several markers, to determine which markers are most useful, and to establish an evidence base for quantitative recommendations for intakes of dietary fibre.
Methods
We did a series of systematic reviews and meta-analyses of prospective studies published from database inception to April 30, 2017, and randomised controlled trials published from database inception to Feb 28, 2018, which reported on indicators of carbohydrate quality and non-communicable disease incidence, mortality, and risk factors. Studies were identified by searches in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We excluded prospective studies and trials reporting on participants with a chronic disease, and weight loss trials or trials involving supplements. Searches, data extraction, and bias assessment were duplicated independently. Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, dose-response testing, and subgroup analyses. The GRADE approach was used to assess quality of evidence.
Findings
Just under 135 million person-years of data from 185 prospective studies and 58 clinical trials with 4635 adult participants were included in the analyses. Observational data suggest a 15–30% decrease in all-cause and cardiovascular related mortality, and incidence of coronary heart disease, stroke incidence and mortality, type 2 diabetes, and colorectal cancer when comparing the highest dietary fibre consumers with the lowest consumers Clinical trials show significantly lower bodyweight, systolic blood pressure, and total cholesterol when comparing higher with lower intakes of dietary fibre. Risk reduction associated with a range of critical outcomes was greatest when daily intake of dietary fibre was between 25 g and 29 g. Dose-response curves suggested that higher intakes of dietary fibre could confer even greater benefit to protect against cardiovascular diseases, type 2 diabetes, and colorectal and breast cancer. Similar findings for whole grain intake were observed. Smaller or no risk reductions were found with the observational data when comparing the effects of diets characterised by low rather than higher glycaemic index or load. The certainty of evidence for relationships between carbohydrate quality and critical outcomes was graded as moderate for dietary fibre, low to moderate for whole grains, and low to very low for dietary glycaemic index and glycaemic load. Data relating to other dietary exposures are scarce.
Interpretation
Findings from prospective studies and clinical trials associated with relatively high intakes of dietary fibre and whole grains were complementary, and striking dose-response evidence indicates that the relationships to several non-communicable diseases could be causal. Implementation of recommendations to increase dietary fibre intake and to replace refined grains with whole grains is expected to benefit human health. A major strength of the study was the ability to examine key indicators of carbohydrate quality in relation to a range of non-communicable disease outcomes from cohort studies and randomised trials in a single study. Our findings are limited to risk reduction in the population at large rather than those with chronic disease.
35margd
Some gut cells slow down metabolism, accelerate cardiovascular disease
NIH/National Heart, Lung and Blood Institute | January 30, 2019
Researchers have discovered how specific cells in the guts of mice slow down metabolism and eventually contribute to obesity, diabetes, hypertension and atherosclerosis. The findings, scientists say, could have important implications for the prevention and treatment of these kinds of metabolic diseases in humans.
...The cells are called intraepithelial T lymphocytes (or natural IELs), and when they are not present, researchers discovered, the metabolism of mice goes into overdrive.
"The mice become metabolically hyperactive and, even when consuming a diet very high in fat and sugar, are able to resist metabolic diseases such as obesity, hypertension, hypercholesterolemia, diabetes, and atherosclerosis," said the study's lead researcher Filip Swirski, Ph.D., an associate professor at Harvard Medical School and Massachusetts General Hospital, Boston.
When natural IELs are present, however, the researchers found that they limit the availability of a type of hormones, incretin GLP-1, that help speed up metabolism. By limiting GLP-1, the natural IELs, in effect, slow down the body's metabolism and conserve the energy it gets from food.
...Swirski's research could eventually shed light on how to prevent and treat cardiovascular disease and other related ailments in humans. The first step is to determine the number and variations of natural IELs in people, then answer key questions. Do individuals with low numbers of IELs get protected against cardiovascular disease? Could blocking IELs reduce their risks?...
https://www.sciencedaily.com/releases/2019/01/190130133201.htm
Story Source:
Filip Swirski et al. 2019. Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease. Nature, 2019 DOI: 10.1038/s41586-018-0849-9 https://www.nature.com/articles/s41586-018-0849-9
Abstract
The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways, how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells—integrin β7+ natural gut intraepithelial T lymphocytes (natural IELs)—that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin β7− mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-12, which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.
NIH/National Heart, Lung and Blood Institute | January 30, 2019
Researchers have discovered how specific cells in the guts of mice slow down metabolism and eventually contribute to obesity, diabetes, hypertension and atherosclerosis. The findings, scientists say, could have important implications for the prevention and treatment of these kinds of metabolic diseases in humans.
...The cells are called intraepithelial T lymphocytes (or natural IELs), and when they are not present, researchers discovered, the metabolism of mice goes into overdrive.
"The mice become metabolically hyperactive and, even when consuming a diet very high in fat and sugar, are able to resist metabolic diseases such as obesity, hypertension, hypercholesterolemia, diabetes, and atherosclerosis," said the study's lead researcher Filip Swirski, Ph.D., an associate professor at Harvard Medical School and Massachusetts General Hospital, Boston.
When natural IELs are present, however, the researchers found that they limit the availability of a type of hormones, incretin GLP-1, that help speed up metabolism. By limiting GLP-1, the natural IELs, in effect, slow down the body's metabolism and conserve the energy it gets from food.
...Swirski's research could eventually shed light on how to prevent and treat cardiovascular disease and other related ailments in humans. The first step is to determine the number and variations of natural IELs in people, then answer key questions. Do individuals with low numbers of IELs get protected against cardiovascular disease? Could blocking IELs reduce their risks?...
https://www.sciencedaily.com/releases/2019/01/190130133201.htm
Story Source:
Filip Swirski et al. 2019. Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease. Nature, 2019 DOI: 10.1038/s41586-018-0849-9 https://www.nature.com/articles/s41586-018-0849-9
Abstract
The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways, how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells—integrin β7+ natural gut intraepithelial T lymphocytes (natural IELs)—that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin β7− mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-12, which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.
36margd
This Appalachian town was America’s ‘fattest city.’ Here’s how it slimmed down.
Brent Cunningham and Jane Black | April 10
...CDC’s latest metropolitan health survey found that the city’s rate of obesity among adults had dropped a whopping 13 points, from 45.5 to 32.6 percent, even as the overall rate in West Virginia remained the highest in the nation. Huntington was no longer America’s fattest city. What happened in Huntington, a city of 47,000 at the intersection of the Rust Belt and Appalachia, offers important lessons for how the nation deals with its obesity problem — which today afflicts nearly 40 percent of adults and 1 in 6 children.
...what’s happening in Huntington: slow, incremental, uneven change in the culture of a community — from where people shop for food to what their kids are served in school to what their mayor and their pastors have to say about choices at mealtime.
...It took years to figure out what would work. In 2012, a group of women opened the Wild Ramp, a food market that runs on consignment, with 80 percent of sales going to local farmers and artisans who drop their goods off, then come back to pick up their checks. This makes sense in Huntington because farming has always been a marginal proposition in the region’s rocky hills and tight hollows. Most farmers have other jobs to pay the bills and, therefore, little time to stand at a farmers market to sell what they grow. It makes sense, too, because Huntington has never really recovered from the collapse of its manufacturing economy, and the market is billed as economic development rather than some yuppified import from the coasts.
...Since it launched, the market has returned some $1.3 million to local farmers and producers. This in a town where the per capita annual income is about $21,500. It has become a hub of activity around locally produced food, with educational programs, a festival and a positive presence in a town that needed one...it has made the idea of fresh, local food — and the healthier way of eating that evokes — a point of pride for residents, rather than an eat-your-broccoli lecture by outside “experts.”
Meanwhile, a much less visible revolution was underway in the public school cafeterias...Rhonda McCoy, the school system’s food service director...tweaked (recipes) to suit local tastes and pass bureaucratic muster. She secured grants to retrofit her kitchens and retrained her cooks, and today more than 80 percent of the food served to students in Cabell County Schools, the district that includes Huntington, is made from scratch.
Huntington’s schools spent more than $67,000 on fresh produce from student and local farmers last year, and they’re on track to buy even more in 2019...kids are more likely to eat vegetables if they know that a friend had a hand in growing them...though the Trump administration last year lowered nutrition standards for grains, flavored milk and sodium in school cafeterias, McCoy continues to run her program under the stricter Obama-era rules.
...still...work to do...But the shift is real, and because it has institutional roots in the community, it is more likely to grow over time. The city now hosts a number of distance runs and has built dozens of miles of bike trails. In 2015, Mayor Steve Williams began a series of “Walks With the Mayor,” in which he and other city officials stroll through neighborhoods to encourage residents to be more active.
...takes time.
...In Huntington, change began not in individual homes but in public spaces: schools, churches, food stores, the mayor’s office...
https://www.washingtonpost.com/outlook/this-appalachian-town-was-americas-fattes...
Brent Cunningham and Jane Black | April 10
...CDC’s latest metropolitan health survey found that the city’s rate of obesity among adults had dropped a whopping 13 points, from 45.5 to 32.6 percent, even as the overall rate in West Virginia remained the highest in the nation. Huntington was no longer America’s fattest city. What happened in Huntington, a city of 47,000 at the intersection of the Rust Belt and Appalachia, offers important lessons for how the nation deals with its obesity problem — which today afflicts nearly 40 percent of adults and 1 in 6 children.
...what’s happening in Huntington: slow, incremental, uneven change in the culture of a community — from where people shop for food to what their kids are served in school to what their mayor and their pastors have to say about choices at mealtime.
...It took years to figure out what would work. In 2012, a group of women opened the Wild Ramp, a food market that runs on consignment, with 80 percent of sales going to local farmers and artisans who drop their goods off, then come back to pick up their checks. This makes sense in Huntington because farming has always been a marginal proposition in the region’s rocky hills and tight hollows. Most farmers have other jobs to pay the bills and, therefore, little time to stand at a farmers market to sell what they grow. It makes sense, too, because Huntington has never really recovered from the collapse of its manufacturing economy, and the market is billed as economic development rather than some yuppified import from the coasts.
...Since it launched, the market has returned some $1.3 million to local farmers and producers. This in a town where the per capita annual income is about $21,500. It has become a hub of activity around locally produced food, with educational programs, a festival and a positive presence in a town that needed one...it has made the idea of fresh, local food — and the healthier way of eating that evokes — a point of pride for residents, rather than an eat-your-broccoli lecture by outside “experts.”
Meanwhile, a much less visible revolution was underway in the public school cafeterias...Rhonda McCoy, the school system’s food service director...tweaked (recipes) to suit local tastes and pass bureaucratic muster. She secured grants to retrofit her kitchens and retrained her cooks, and today more than 80 percent of the food served to students in Cabell County Schools, the district that includes Huntington, is made from scratch.
Huntington’s schools spent more than $67,000 on fresh produce from student and local farmers last year, and they’re on track to buy even more in 2019...kids are more likely to eat vegetables if they know that a friend had a hand in growing them...though the Trump administration last year lowered nutrition standards for grains, flavored milk and sodium in school cafeterias, McCoy continues to run her program under the stricter Obama-era rules.
...still...work to do...But the shift is real, and because it has institutional roots in the community, it is more likely to grow over time. The city now hosts a number of distance runs and has built dozens of miles of bike trails. In 2015, Mayor Steve Williams began a series of “Walks With the Mayor,” in which he and other city officials stroll through neighborhoods to encourage residents to be more active.
...takes time.
...In Huntington, change began not in individual homes but in public spaces: schools, churches, food stores, the mayor’s office...
https://www.washingtonpost.com/outlook/this-appalachian-town-was-americas-fattes...
37margd
This Genetic Mutation Makes People Feel Full — All the Time
Gina Kolata | April 18, 2019
Two new studies confirm that weight control is often the result of genetics, not willpower.
Mutations in the MC4R gene usually lead to obesity by preventing a sense of fullness. But one such mutation leaves people uninterested in eating, scientists report.
The study subjects had been thin all their lives, and not because they had unusual metabolisms. They just did not care much about food.
They never ate enormous amounts, never obsessed on the next meal. Now, a group of researchers in Britain may have found the reason.
The people carry a genetic alteration that mutes appetite. It also greatly reduces their chances of getting diabetes or heart disease.
The scientists’ study, published on Thursday in the journal Cell, relied on data from the U.K. Biobank, which includes a half million people aged 40 to 69. Participants have provided DNA samples and medical records, and have allowed researchers to track their health over years.
A second study in the same journal also used data from this population to develop a genetic risk score for obesity. It can help predict, as early as childhood, who is at high risk for a lifetime of obesity and who is not.
Together, the studies confirm a truth that researchers wish more people understood. There are biological reasons that some struggle mightily with their weight and others do not, and the biological impacts often are seen on appetite, not metabolism. People who gain too much weight or fight to stay thin feel hungrier than naturally thin people...
...in some thin people, the MC4R gene is always turned on...About 6 percent of the population carries such protective mutations...an obvious target for drugs to protect against obesity...
https://www.nytimes.com/2019/04/18/health/genetics-weight-obesity.html
-----------------------------------------------------------------------------------------------
Luca A. Lotta et al. 2019. Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.
Cell Volume 177, ISSUE 3, P597-607.e9, April 18, 2019. https://doi.org/10.1016/j.cell.2019.03.044
https://www.cell.com/cell/fulltext/S0092-8674(19)30345-9
Highlights
• 61 variants in the Melanocortin-4 Receptor gene were found in 0.5 million people
• Variants causing a gain of function were associated with protection from obesity
• Variants biased toward β-arrestin signaling mediated the protective effects
Summary
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor whose disruption causes obesity. We functionally characterized 61 MC4R variants identified in 0.5 million people from UK Biobank and examined their associations with body mass index (BMI) and obesity-related cardiometabolic diseases. We found that the maximal efficacy of β-arrestin recruitment to MC4R, rather than canonical Gαs-mediated cyclic adenosine-monophosphate production, explained 88% of the variance in the association of MC4R variants with BMI. While most MC4R variants caused loss of function, a subset caused gain of function; these variants were associated with significantly lower BMI and lower odds of obesity, type 2 diabetes, and coronary artery disease. Protective associations were driven by MC4R variants exhibiting signaling bias toward β-arrestin recruitment and increased mitogen-activated protein kinase pathway activation. Harnessing β-arrestin-biased MC4R signaling may represent an effective strategy for weight loss and the treatment of obesity-related cardiometabolic diseases.
Gina Kolata | April 18, 2019
Two new studies confirm that weight control is often the result of genetics, not willpower.
Mutations in the MC4R gene usually lead to obesity by preventing a sense of fullness. But one such mutation leaves people uninterested in eating, scientists report.
The study subjects had been thin all their lives, and not because they had unusual metabolisms. They just did not care much about food.
They never ate enormous amounts, never obsessed on the next meal. Now, a group of researchers in Britain may have found the reason.
The people carry a genetic alteration that mutes appetite. It also greatly reduces their chances of getting diabetes or heart disease.
The scientists’ study, published on Thursday in the journal Cell, relied on data from the U.K. Biobank, which includes a half million people aged 40 to 69. Participants have provided DNA samples and medical records, and have allowed researchers to track their health over years.
A second study in the same journal also used data from this population to develop a genetic risk score for obesity. It can help predict, as early as childhood, who is at high risk for a lifetime of obesity and who is not.
Together, the studies confirm a truth that researchers wish more people understood. There are biological reasons that some struggle mightily with their weight and others do not, and the biological impacts often are seen on appetite, not metabolism. People who gain too much weight or fight to stay thin feel hungrier than naturally thin people...
...in some thin people, the MC4R gene is always turned on...About 6 percent of the population carries such protective mutations...an obvious target for drugs to protect against obesity...
https://www.nytimes.com/2019/04/18/health/genetics-weight-obesity.html
-----------------------------------------------------------------------------------------------
Luca A. Lotta et al. 2019. Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.
Cell Volume 177, ISSUE 3, P597-607.e9, April 18, 2019. https://doi.org/10.1016/j.cell.2019.03.044
https://www.cell.com/cell/fulltext/S0092-8674(19)30345-9
Highlights
• 61 variants in the Melanocortin-4 Receptor gene were found in 0.5 million people
• Variants causing a gain of function were associated with protection from obesity
• Variants biased toward β-arrestin signaling mediated the protective effects
Summary
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor whose disruption causes obesity. We functionally characterized 61 MC4R variants identified in 0.5 million people from UK Biobank and examined their associations with body mass index (BMI) and obesity-related cardiometabolic diseases. We found that the maximal efficacy of β-arrestin recruitment to MC4R, rather than canonical Gαs-mediated cyclic adenosine-monophosphate production, explained 88% of the variance in the association of MC4R variants with BMI. While most MC4R variants caused loss of function, a subset caused gain of function; these variants were associated with significantly lower BMI and lower odds of obesity, type 2 diabetes, and coronary artery disease. Protective associations were driven by MC4R variants exhibiting signaling bias toward β-arrestin recruitment and increased mitogen-activated protein kinase pathway activation. Harnessing β-arrestin-biased MC4R signaling may represent an effective strategy for weight loss and the treatment of obesity-related cardiometabolic diseases.
38margd
How Useful Would A Genetic Test For Obesity Risk Be?
Richard Harris | May 6, 2019
Heard on Morning Edition (Audio)
...untold thousands of genes apparently play a role in increasing obesity risk.
Many of those gene variants contribute a miniscule risk. Sekar Kathiresan, a cardiologist at Harvard and a geneticist at the Broad Institute, set out to see whether he and his team could find a bunch of these genetic variants and add up their effects. The goal was to identify genetic patterns that put people at the highest risk.
This genetic information "could explain why somebody's so big, why they have so much trouble keeping their weight down," Kathiresan says.
His team identified more than 2 million DNA variants of potential interest. He figures most of those variants are irrelevant, but his hunch is, hidden somewhere in there are a few thousand changes that each contribute at least a tiny bit to a person's risk of developing obesity.
No single gene can do much to move the needle. But he says the composite result, called a polygenic risk score, is still potentially useful. Those with the highest risk scores were more likely to be severely obese (with a body mass index over 40). In fact, 43% of the people with the highest genetic scores were obese.
But the score is far from perfect. For instance, 17% of the people with the highest scores had normal body weights.
"The impact of the genetics — and this was a huge surprise to us as well — starts very early in life, in the preschool years, around the age of 3," Kathiresan says...
...finding suggests prevention efforts are more likely to succeed if they also start in childhood. Kathiresan has a more philosophical takeaway from his work as well.
"I hope this work will hopefully destigmatize obesity and make it very similar to every other disease, which is a combination of both lifestyle and genetics."..
_______________________________________________________________________________________________
Amit V. Khera et al. 2019. Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. Cell. Volume 177, ISSUE 3, P587-596.e9, April 18, 2019.
DOI:https://doi.org/10.1016/j.cell.2019.03.028 . https://www.cell.com/cell/pdf/S0092-8674(19)30290-9.pdf
Highlights
• A genome-wide polygenic score can quantify inherited susceptibility to obesity
• Polygenic score effect on weight emerges early in life and increases into adulthood
• Effect of polygenic score can be similar to a rare, monogenic obesity mutation
• High polygenic score is a strong risk factor for severe obesity and associated diseases
Summary
Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment.
Richard Harris | May 6, 2019
Heard on Morning Edition (Audio)
...untold thousands of genes apparently play a role in increasing obesity risk.
Many of those gene variants contribute a miniscule risk. Sekar Kathiresan, a cardiologist at Harvard and a geneticist at the Broad Institute, set out to see whether he and his team could find a bunch of these genetic variants and add up their effects. The goal was to identify genetic patterns that put people at the highest risk.
This genetic information "could explain why somebody's so big, why they have so much trouble keeping their weight down," Kathiresan says.
His team identified more than 2 million DNA variants of potential interest. He figures most of those variants are irrelevant, but his hunch is, hidden somewhere in there are a few thousand changes that each contribute at least a tiny bit to a person's risk of developing obesity.
No single gene can do much to move the needle. But he says the composite result, called a polygenic risk score, is still potentially useful. Those with the highest risk scores were more likely to be severely obese (with a body mass index over 40). In fact, 43% of the people with the highest genetic scores were obese.
But the score is far from perfect. For instance, 17% of the people with the highest scores had normal body weights.
"The impact of the genetics — and this was a huge surprise to us as well — starts very early in life, in the preschool years, around the age of 3," Kathiresan says...
...finding suggests prevention efforts are more likely to succeed if they also start in childhood. Kathiresan has a more philosophical takeaway from his work as well.
"I hope this work will hopefully destigmatize obesity and make it very similar to every other disease, which is a combination of both lifestyle and genetics."..
_______________________________________________________________________________________________
Amit V. Khera et al. 2019. Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. Cell. Volume 177, ISSUE 3, P587-596.e9, April 18, 2019.
DOI:https://doi.org/10.1016/j.cell.2019.03.028 . https://www.cell.com/cell/pdf/S0092-8674(19)30290-9.pdf
Highlights
• A genome-wide polygenic score can quantify inherited susceptibility to obesity
• Polygenic score effect on weight emerges early in life and increases into adulthood
• Effect of polygenic score can be similar to a rare, monogenic obesity mutation
• High polygenic score is a strong risk factor for severe obesity and associated diseases
Summary
Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment.
39margd
A small preliminary study, not yet peer-reviewed, more research planned:
A gut bacteria transplant may not help you lose weight
Getting intestinal microbes from a lean person didn’t help obese people drop pounds
Tina Hesman Saey | May 9, 2019
...In a preliminary study, obese people got either capsules containing gut microbes from a lean person or placebo pills. Microbes from the lean donor took hold in the guts of the obese recipients. But early results suggest that the bacteria didn’t change the volunteers’ weight or levels of a hormone that helps signal fullness...
People with obesity often have different types of gut microbes than lean people do. And previous studies with lab animals and anecdotal evidence from people have suggested that transfers of intestinal bacteria and other microbes — collectively known as the gut microbiome — from a donor to a recipient may lead to weight loss or gain, depending on whether the donor was lean or obese. So the researchers reasoned that giving obese people gut microbes from a lean person, known as a fecal or intestinal microbiome transplant, might help overweight people control appetite and shed pounds.
...When people eat fiber, gut microbes process that fiber into short chain fatty acids. Those molecules cause the small intestine to make GLP-1, which in turn tells the brain that the person has had enough to eat. Other weight loss studies have indicated that GLP-1 levels change as people lose weight.
...no change in the satiety protein between the transplant and placebo groups. There was also no indication that the bacteria led to weight loss.
But people who got the lean microbes increased production of certain bile acids, which help break down fats. Providing new gut microbes that make bile-acid-processing enzymes may alter the metabolism of fat in obese patients
In the United States, the Food and Drug Administration allows intestinal microbiome transplants for treating people with infections with Clostridium difficile for whom other treatments have failed. C. diff is a severe bacterial infection that takes hold when people’s normal gut microbes have been ravaged by antibiotics. The bacteria can cause symptoms ranging from diarrhea to life-threatening inflammation of the intestines and other organs. In those instances, intestinal microbe transplants can save lives.
So far, gut microbe transplants to treat diabetes have made some obese people with the disease more sensitive to insulin. But that hasn’t really helped them lose weight
...it’s still too early to determine what role the microbiome plays in obesity. Researchers aren’t yet sure what a healthy microbiome is, for example. Nor do they know or whether the microbes in the colon (those are the ones transferred in this and other fecal microbiome transplants) or those in the small intestine play a bigger role in determining body weight...may need to alter the dose of lean microbes or tweak the treatments in other ways to maximize the results.
Citations
J.R. Allegretti et al. Fecal microbiota transplantation for the treatment of obesity: a randomized, placebo-controlled pilot trial. Digestive Disease Week 2019. May 20, 2019, San Diego, Calif.
Further Reading
T.H. Saey. The right mix of gut microbes relieves autism symptoms in the long run. Science News. Vol. 194, August 18, 2018, p. 11.
B. Brookshire. To regulate fecal transplants, FDA has to first answer a serious question: What is poop? Science News Online, May 18, 2018.
T.H. Saey. Gut fungi might be linked to obesity and inflammatory bowel disorders. Science News Online, October 16, 2017.
https://www.sciencenews.org/article/fecal-transplant-gut-bacteria-microbiome-wei...
A gut bacteria transplant may not help you lose weight
Getting intestinal microbes from a lean person didn’t help obese people drop pounds
Tina Hesman Saey | May 9, 2019
...In a preliminary study, obese people got either capsules containing gut microbes from a lean person or placebo pills. Microbes from the lean donor took hold in the guts of the obese recipients. But early results suggest that the bacteria didn’t change the volunteers’ weight or levels of a hormone that helps signal fullness...
People with obesity often have different types of gut microbes than lean people do. And previous studies with lab animals and anecdotal evidence from people have suggested that transfers of intestinal bacteria and other microbes — collectively known as the gut microbiome — from a donor to a recipient may lead to weight loss or gain, depending on whether the donor was lean or obese. So the researchers reasoned that giving obese people gut microbes from a lean person, known as a fecal or intestinal microbiome transplant, might help overweight people control appetite and shed pounds.
...When people eat fiber, gut microbes process that fiber into short chain fatty acids. Those molecules cause the small intestine to make GLP-1, which in turn tells the brain that the person has had enough to eat. Other weight loss studies have indicated that GLP-1 levels change as people lose weight.
...no change in the satiety protein between the transplant and placebo groups. There was also no indication that the bacteria led to weight loss.
But people who got the lean microbes increased production of certain bile acids, which help break down fats. Providing new gut microbes that make bile-acid-processing enzymes may alter the metabolism of fat in obese patients
In the United States, the Food and Drug Administration allows intestinal microbiome transplants for treating people with infections with Clostridium difficile for whom other treatments have failed. C. diff is a severe bacterial infection that takes hold when people’s normal gut microbes have been ravaged by antibiotics. The bacteria can cause symptoms ranging from diarrhea to life-threatening inflammation of the intestines and other organs. In those instances, intestinal microbe transplants can save lives.
So far, gut microbe transplants to treat diabetes have made some obese people with the disease more sensitive to insulin. But that hasn’t really helped them lose weight
...it’s still too early to determine what role the microbiome plays in obesity. Researchers aren’t yet sure what a healthy microbiome is, for example. Nor do they know or whether the microbes in the colon (those are the ones transferred in this and other fecal microbiome transplants) or those in the small intestine play a bigger role in determining body weight...may need to alter the dose of lean microbes or tweak the treatments in other ways to maximize the results.
Citations
J.R. Allegretti et al. Fecal microbiota transplantation for the treatment of obesity: a randomized, placebo-controlled pilot trial. Digestive Disease Week 2019. May 20, 2019, San Diego, Calif.
Further Reading
T.H. Saey. The right mix of gut microbes relieves autism symptoms in the long run. Science News. Vol. 194, August 18, 2018, p. 11.
B. Brookshire. To regulate fecal transplants, FDA has to first answer a serious question: What is poop? Science News Online, May 18, 2018.
T.H. Saey. Gut fungi might be linked to obesity and inflammatory bowel disorders. Science News Online, October 16, 2017.
https://www.sciencenews.org/article/fecal-transplant-gut-bacteria-microbiome-wei...
402wonderY
>39 margd: Fascinating. I've read a bit on the non-technical side. It's good to have more detail.
41margd
Rural areas drive increases in global obesity
The global rise in the prevalence of obesity has been seen as an urban problem. A large-scale study challenges this view by showing that weight gain in rural areas is the main factor currently driving the obesity epidemic.
Barry M. Popkin | 08 May 2019
...the paper* by the NCD Risk Factor Collaboration is ground-breaking, because it pulls together the latest data from almost all countries to comprehensively examine global BMI trends. The results show that the levels of overweight and obesity are already greater in rural than in urban areas in all high-income countries, and also suggest that the rate of change in many LMICs is such that the levels of overweight and obesity in rural areas will soon match, if not exceed, those in urban areas. Rural hunger, wasting and stunting are rapidly being replaced by overweight and obesity in most regions of the world except sub-Saharan Africa, South Asia and a small number of countries in other areas.
This finding is fundamental, because the main focus of geographically targeted obesity-prevention programmes and policies around the globe has been to address urban obesity. Examples of urban-focused interventions include physical-activity policies such as the ciclovias of Latin America that close urban streets to stimulate walking and cycling; the construction of cycle paths in urban areas; the design of urban buildings to enhance movement; and the focus on creating spaces for walking and playing in cities, including creating parks. Initiatives that involve working with retailers and shops that sell food have also mostly taken place in cities. Apart from a small number of policies, such as the provision of government-sponsored shops selling cheap, healthier food in remote rural areas in Mexico, rural populations have been largely ignored.
The study by the NCD Risk Factor Collaboration challenges us to create programmes and policies that are rurally focused to prevent increased weight gain — a major global gap. Several fiscal and regulatory approaches can reach rural areas globally. These range from programmes that combine comprehensive marketing controls, school-food controls and labels on ultra-processed foods, such as those instituted in Chile, to the taxation of unhealthy ultra-processed foods and beverages, as in Mexico. These are national programmes that require national legislation and are being implemented in an increasing number of LMICs. However, countries must coordinate multiple regulatory and fiscal programmes similar to those in Chile to truly have an impact on people’s behaviour.
https://www.nature.com/articles/d41586-019-01182-x
-------------------------------------------------------------------------------------------------------------
* NCD Risk Factor Collaboration (NCD-RisC). 2019. Rising rural body-mass index is the main driver of the global obesity epidemic in adults. Nature volume 569, pages 260–264 (May 8, 2019) | https://www.nature.com/articles/s41586-019-1171-x
Abstract
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
The global rise in the prevalence of obesity has been seen as an urban problem. A large-scale study challenges this view by showing that weight gain in rural areas is the main factor currently driving the obesity epidemic.
Barry M. Popkin | 08 May 2019
...the paper* by the NCD Risk Factor Collaboration is ground-breaking, because it pulls together the latest data from almost all countries to comprehensively examine global BMI trends. The results show that the levels of overweight and obesity are already greater in rural than in urban areas in all high-income countries, and also suggest that the rate of change in many LMICs is such that the levels of overweight and obesity in rural areas will soon match, if not exceed, those in urban areas. Rural hunger, wasting and stunting are rapidly being replaced by overweight and obesity in most regions of the world except sub-Saharan Africa, South Asia and a small number of countries in other areas.
This finding is fundamental, because the main focus of geographically targeted obesity-prevention programmes and policies around the globe has been to address urban obesity. Examples of urban-focused interventions include physical-activity policies such as the ciclovias of Latin America that close urban streets to stimulate walking and cycling; the construction of cycle paths in urban areas; the design of urban buildings to enhance movement; and the focus on creating spaces for walking and playing in cities, including creating parks. Initiatives that involve working with retailers and shops that sell food have also mostly taken place in cities. Apart from a small number of policies, such as the provision of government-sponsored shops selling cheap, healthier food in remote rural areas in Mexico, rural populations have been largely ignored.
The study by the NCD Risk Factor Collaboration challenges us to create programmes and policies that are rurally focused to prevent increased weight gain — a major global gap. Several fiscal and regulatory approaches can reach rural areas globally. These range from programmes that combine comprehensive marketing controls, school-food controls and labels on ultra-processed foods, such as those instituted in Chile, to the taxation of unhealthy ultra-processed foods and beverages, as in Mexico. These are national programmes that require national legislation and are being implemented in an increasing number of LMICs. However, countries must coordinate multiple regulatory and fiscal programmes similar to those in Chile to truly have an impact on people’s behaviour.
https://www.nature.com/articles/d41586-019-01182-x
-------------------------------------------------------------------------------------------------------------
* NCD Risk Factor Collaboration (NCD-RisC). 2019. Rising rural body-mass index is the main driver of the global obesity epidemic in adults. Nature volume 569, pages 260–264 (May 8, 2019) | https://www.nature.com/articles/s41586-019-1171-x
Abstract
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
42margd
NIH study finds heavily processed foods cause overeating and weight gain
Thursday, May 16, 2019
Small-scale trial is the first randomized, controlled research of its kind.
People eating ultra-processed foods ate more calories and gained more weight than when they ate a minimally processed diet, according to results from a National Institutes of Health study. The difference occurred even though meals provided to the volunteers in both the ultra-processed and minimally processed diets had the same number of calories and macronutrients. The results were published in Cell Metabolism.*
...ultra-processed foods as defined by the NOVA classification system. This system considers foods “ultra-processed” if they have ingredients predominantly found in industrial food manufacturing, such as hydrogenated oils, high-fructose corn syrup, flavoring agents, and emulsifiers.
...an ultra-processed breakfast might consist of a bagel with cream cheese and turkey bacon, while the unprocessed breakfast was oatmeal with bananas, walnuts, and skim milk
...The ultra-processed and unprocessed meals had the same amounts of calories, sugars, fiber, fat, and carbohydrates, and participants could eat as much or as little as they wanted...
https://www.nih.gov/news-events/news-releases/nih-study-finds-heavily-processed-...
_______________________________________________________________________
* Hall KD, Ayuketah A, Bernstein S, et al. 2019. Ultra-processed diets cause excess calorie intake and weight gain: A one-month inpatient randomized controlled trial of ad libitum food intake. Cell Metabolism (link is external). May 16, 2019. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30248-7
Highlights
• 20 inpatient adults received ultra-processed and unprocessed diets for 14 days each
• Diets were matched for presented calories, sugar, fat, fiber, and macronutrients
• Ad libitum intake was ∼500 kcal/day more on the ultra-processed versus unprocessed diet
• Body weight changes were highly correlated with diet differences in energy intake
Summary
We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean ± SE) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 ± 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 ± 54 kcal/day; p less than 0.0001) and fat (230 ± 53 kcal/day; p = 0.0004), but not protein (−2 ± 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p less than 0.0001), with participants gaining 0.9 ± 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 ± 0.3 kg (p = 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.
ETA_________________________________________________________________________
Processed foods lead to weight gain, but it's about more than calories
Yella Hewings-Martin PhD | May 17, 2019
https://www.medicalnewstoday.com/articles/325194.php
Thursday, May 16, 2019
Small-scale trial is the first randomized, controlled research of its kind.
People eating ultra-processed foods ate more calories and gained more weight than when they ate a minimally processed diet, according to results from a National Institutes of Health study. The difference occurred even though meals provided to the volunteers in both the ultra-processed and minimally processed diets had the same number of calories and macronutrients. The results were published in Cell Metabolism.*
...ultra-processed foods as defined by the NOVA classification system. This system considers foods “ultra-processed” if they have ingredients predominantly found in industrial food manufacturing, such as hydrogenated oils, high-fructose corn syrup, flavoring agents, and emulsifiers.
...an ultra-processed breakfast might consist of a bagel with cream cheese and turkey bacon, while the unprocessed breakfast was oatmeal with bananas, walnuts, and skim milk
...The ultra-processed and unprocessed meals had the same amounts of calories, sugars, fiber, fat, and carbohydrates, and participants could eat as much or as little as they wanted...
https://www.nih.gov/news-events/news-releases/nih-study-finds-heavily-processed-...
_______________________________________________________________________
* Hall KD, Ayuketah A, Bernstein S, et al. 2019. Ultra-processed diets cause excess calorie intake and weight gain: A one-month inpatient randomized controlled trial of ad libitum food intake. Cell Metabolism (link is external). May 16, 2019. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30248-7
Highlights
• 20 inpatient adults received ultra-processed and unprocessed diets for 14 days each
• Diets were matched for presented calories, sugar, fat, fiber, and macronutrients
• Ad libitum intake was ∼500 kcal/day more on the ultra-processed versus unprocessed diet
• Body weight changes were highly correlated with diet differences in energy intake
Summary
We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean ± SE) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 ± 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 ± 54 kcal/day; p less than 0.0001) and fat (230 ± 53 kcal/day; p = 0.0004), but not protein (−2 ± 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p less than 0.0001), with participants gaining 0.9 ± 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 ± 0.3 kg (p = 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.
ETA_________________________________________________________________________
Processed foods lead to weight gain, but it's about more than calories
Yella Hewings-Martin PhD | May 17, 2019
https://www.medicalnewstoday.com/articles/325194.php
43margd
Seven ways to do intermittent fasting
Jayne Leonard | Last reviewed Thu 28 June 2018
...1. Fast for 12 hours a day...According to some researchers, fasting for 10–16 hours can cause the body to turn its fat stores into energy, which releases ketones into the bloodstream...
...2. Fasting for 16 hours (14 for women)...A study on mice found that limiting the feeding window to 8 hours protected them from obesity, inflammation, diabetes, and liver disease, even when they ate the same total number of calories as mice that ate whenever they wished...
...3. Fasting for 2 days a week...During the 2 fasting days, men generally consume 600 calories and women 500 calories...There should be at least 1 non-fasting day between fasting days...A study involving 107 overweight or obese women found that restricting calories twice weekly and continuous calorie restriction both led to similar weight loss...reduced insulin levels and improved insulin sensitivity among participants...23 overweight women...lost 4.8 percent of their body weight and 8.0 percent of their total body fat. However, these measurements returned to normal for most of the women after 5 days of normal eating.(?)
...4. Alternate day fasting...For some people, alternate day fasting means a complete avoidance of solid foods on fasting days, while other people allow up to 500 calories...32 participants (in one study) lost an average of 5.2 kilograms (kg), or just over 11 pounds (lb), over a 12-week period...may not be suitable for beginners or those with certain medical conditions...may also be difficult to maintain this type of fasting in the long term.
...5. A weekly 24-hour fast...may cause fatigue, headaches, or irritability. Many people find that these effects become less extreme over time as the body adjusts to this new pattern of eating.
...6. Meal skipping...eat when they are hungry and skip meals when they are not...
...7. The Warrior Diet...extreme...involves eating very little, usually just a few servings of raw fruit and vegetables, during a 20-hour fasting window, then eating one large meal at night. The eating window is usually only around 4 hours...
Tips for maintaining intermittent fasting
Yoga and light exercise may help to make intermittent fasting easier.
Yoga and light exercise may help to make intermittent fasting easier.
It can be challenging to stick to an intermittent fasting program.
...Stay hydrated. Drink lots of water and calorie-free drinks, such as herbal teas, throughout the day.
...Avoiding obsessing over food.
...Rest and relax.
...Making every calorie count...beans, lentils, eggs, fish, nuts, and avocado.
...Eat high-volume foods...popcorn, raw vegetables, and fruits with high water content, such as grapes and melon.
...Increasing the taste without the calories...garlic, herbs, spices, or vinegar.
...If a person is prone to disordered eating, these approaches may exacerbate their unhealthy relationship with food.
...People with health conditions, including diabetes, should speak to a doctor before attempting any form of fasting.
...essential to eat a healthful and balanced diet on non-fasting days.
...Q: Are all types of intermittent fasting styles safe?
A: People have practiced fasting for thousands of years, but its safety depends more on who is doing the fasting than the style of fasting itself. People who have malabsorption, are at risk of low blood sugar, or have other medical conditions should seek the counsel of their healthcare provider. While most people can practice many fasting styles safely, extreme types of intermittent fasting, such as the Warrior Diet, can lead to inadequate intake of nutrients such as fiber, vitamins, and minerals. Therefore, people should approach this style of fasting with caution.
https://www.medicalnewstoday.com/articles/322293.php
Jayne Leonard | Last reviewed Thu 28 June 2018
...1. Fast for 12 hours a day...According to some researchers, fasting for 10–16 hours can cause the body to turn its fat stores into energy, which releases ketones into the bloodstream...
...2. Fasting for 16 hours (14 for women)...A study on mice found that limiting the feeding window to 8 hours protected them from obesity, inflammation, diabetes, and liver disease, even when they ate the same total number of calories as mice that ate whenever they wished...
...3. Fasting for 2 days a week...During the 2 fasting days, men generally consume 600 calories and women 500 calories...There should be at least 1 non-fasting day between fasting days...A study involving 107 overweight or obese women found that restricting calories twice weekly and continuous calorie restriction both led to similar weight loss...reduced insulin levels and improved insulin sensitivity among participants...23 overweight women...lost 4.8 percent of their body weight and 8.0 percent of their total body fat. However, these measurements returned to normal for most of the women after 5 days of normal eating.(?)
...4. Alternate day fasting...For some people, alternate day fasting means a complete avoidance of solid foods on fasting days, while other people allow up to 500 calories...32 participants (in one study) lost an average of 5.2 kilograms (kg), or just over 11 pounds (lb), over a 12-week period...may not be suitable for beginners or those with certain medical conditions...may also be difficult to maintain this type of fasting in the long term.
...5. A weekly 24-hour fast...may cause fatigue, headaches, or irritability. Many people find that these effects become less extreme over time as the body adjusts to this new pattern of eating.
...6. Meal skipping...eat when they are hungry and skip meals when they are not...
...7. The Warrior Diet...extreme...involves eating very little, usually just a few servings of raw fruit and vegetables, during a 20-hour fasting window, then eating one large meal at night. The eating window is usually only around 4 hours...
Tips for maintaining intermittent fasting
Yoga and light exercise may help to make intermittent fasting easier.
Yoga and light exercise may help to make intermittent fasting easier.
It can be challenging to stick to an intermittent fasting program.
...Stay hydrated. Drink lots of water and calorie-free drinks, such as herbal teas, throughout the day.
...Avoiding obsessing over food.
...Rest and relax.
...Making every calorie count...beans, lentils, eggs, fish, nuts, and avocado.
...Eat high-volume foods...popcorn, raw vegetables, and fruits with high water content, such as grapes and melon.
...Increasing the taste without the calories...garlic, herbs, spices, or vinegar.
...If a person is prone to disordered eating, these approaches may exacerbate their unhealthy relationship with food.
...People with health conditions, including diabetes, should speak to a doctor before attempting any form of fasting.
...essential to eat a healthful and balanced diet on non-fasting days.
...Q: Are all types of intermittent fasting styles safe?
A: People have practiced fasting for thousands of years, but its safety depends more on who is doing the fasting than the style of fasting itself. People who have malabsorption, are at risk of low blood sugar, or have other medical conditions should seek the counsel of their healthcare provider. While most people can practice many fasting styles safely, extreme types of intermittent fasting, such as the Warrior Diet, can lead to inadequate intake of nutrients such as fiber, vitamins, and minerals. Therefore, people should approach this style of fasting with caution.
https://www.medicalnewstoday.com/articles/322293.php
44sashame
while im sure there r many ppl in this group who appreciate ur enthusiasm for copy-pasting glosses of single studies relating to diet and weight, have u considered that u r contributing to the general breakdown of political discussion on this......... political discussion group
like, mb create a "fun facts and recent articles with little to no commentary or discussion" group?
like, mb create a "fun facts and recent articles with little to no commentary or discussion" group?
46mamzel
>44 sashame: As on other threads, I don't seem to see any contributions you make to the discussion.
47margd
Immune system defects seem to contribute to obesity in mice
Similar changes that alter the microbiome and change fat uptake may be at work in people too
Tina Hesman Saey | July 25, 2019
Mice gained weight and developed health problems when they carried a genetic defect that dampens some immune functions...The immune problems were linked to shifts in the gut microbiome — the collection of friendly bacteria and other microbes living in the intestines. Altering the gut microbe mix, particularly in the small intestine, may lead to increased absorption of fat from the diet...
...(June Round, a microbiome researcher at the University of Utah School of Medicine) and colleagues noticed that mice with a defect in the Myd88 gene started gaining weight at about 5 months old. By about a year old, those mice, which lack Myd88 protein in immune cells called T cells, weighed up to 60 grams — about twice as much as a normal mouse. The mutant mice also had developed metabolic problems associated with obesity, such as insulin resistance, a hallmark of type 2 diabetes in people.
Those mice lacking Myd88 had reduced activity of a subset of specialized T cells called T follicular helper cells. These helper cells tell other immune cells called B cells to make antibodies against certain microbes. The mice also made fewer IgA antibodies aimed at controlling certain microbes.
Obese mice had fewer types and lower numbers of Clostridia bacteria and more Desulfovibrio bacteria in their intestines, particularly the small intestine...pattern also has been seen in obese people and people with type 2 diabetes. Some Clostridia species in the Myd88 mutant mice were coated with more IgA antibodies, suggesting those bacteria were inappropriately targeted for destruction. But other Clostridia species had fewer IgA antibodies clinging to them, perhaps hampering their ability to effectively colonize the intestine. Desulfovibrio also was more heavily antibody-coated than usual, but the researchers aren’t sure if or how that aids its growth.
Giving fat mice more Clostridia led to weight loss. But the researchers couldn’t make normal mice fat just by giving them Desulfovibrio, probably because the immune system in normal mice can keep the bacteria in check...
Altered microbiomes may affect how much fat is absorbed in the small intestine. Giving Myd88 mutant mice extra Clostridia reduced the production of a protein involved in fat absorption. But giving the mice Desulfovibrio had the opposite effect, increasing the protein’s production. Those results suggest that Clostridia protect against obesity, while Desulfovibrio promotes it.
...Lora Hooper, a microbiologist and immunologist at the University of Texas Southwestern Medical Center in Dallas...“Why is our microbiome in charge of how much lipid (fat) we take up?” She doubts that Clostridia evolved to protect against obesity, a relatively modern problem. Instead, she speculates, ramped up fat absorption may have evolved to meet the body’s increased energy needs when dealing with pathogens or overgrowth of Desulfovibrio and other gut bacteria.
Citations
C. Petersen et al. T cell–mediated regulation of the microbiota protects against obesity. Science. Vol. 365, July 26, 2019, p. 340. doi: 10.1126/science.aat9351 https://science.sciencemag.org/content/365/6451/eaat9351
Y. Wang and L.V. Hooper. Immune control of the microbiota prevents obesity. Science. Vol. 365, July 26, 2019, p. 316. https://science.sciencemag.org/content/365/6451/316...
https://www.sciencenews.org/article/immune-system-defects-seem-contribute-obesit...
Similar changes that alter the microbiome and change fat uptake may be at work in people too
Tina Hesman Saey | July 25, 2019
Mice gained weight and developed health problems when they carried a genetic defect that dampens some immune functions...The immune problems were linked to shifts in the gut microbiome — the collection of friendly bacteria and other microbes living in the intestines. Altering the gut microbe mix, particularly in the small intestine, may lead to increased absorption of fat from the diet...
...(June Round, a microbiome researcher at the University of Utah School of Medicine) and colleagues noticed that mice with a defect in the Myd88 gene started gaining weight at about 5 months old. By about a year old, those mice, which lack Myd88 protein in immune cells called T cells, weighed up to 60 grams — about twice as much as a normal mouse. The mutant mice also had developed metabolic problems associated with obesity, such as insulin resistance, a hallmark of type 2 diabetes in people.
Those mice lacking Myd88 had reduced activity of a subset of specialized T cells called T follicular helper cells. These helper cells tell other immune cells called B cells to make antibodies against certain microbes. The mice also made fewer IgA antibodies aimed at controlling certain microbes.
Obese mice had fewer types and lower numbers of Clostridia bacteria and more Desulfovibrio bacteria in their intestines, particularly the small intestine...pattern also has been seen in obese people and people with type 2 diabetes. Some Clostridia species in the Myd88 mutant mice were coated with more IgA antibodies, suggesting those bacteria were inappropriately targeted for destruction. But other Clostridia species had fewer IgA antibodies clinging to them, perhaps hampering their ability to effectively colonize the intestine. Desulfovibrio also was more heavily antibody-coated than usual, but the researchers aren’t sure if or how that aids its growth.
Giving fat mice more Clostridia led to weight loss. But the researchers couldn’t make normal mice fat just by giving them Desulfovibrio, probably because the immune system in normal mice can keep the bacteria in check...
Altered microbiomes may affect how much fat is absorbed in the small intestine. Giving Myd88 mutant mice extra Clostridia reduced the production of a protein involved in fat absorption. But giving the mice Desulfovibrio had the opposite effect, increasing the protein’s production. Those results suggest that Clostridia protect against obesity, while Desulfovibrio promotes it.
...Lora Hooper, a microbiologist and immunologist at the University of Texas Southwestern Medical Center in Dallas...“Why is our microbiome in charge of how much lipid (fat) we take up?” She doubts that Clostridia evolved to protect against obesity, a relatively modern problem. Instead, she speculates, ramped up fat absorption may have evolved to meet the body’s increased energy needs when dealing with pathogens or overgrowth of Desulfovibrio and other gut bacteria.
Citations
C. Petersen et al. T cell–mediated regulation of the microbiota protects against obesity. Science. Vol. 365, July 26, 2019, p. 340. doi: 10.1126/science.aat9351 https://science.sciencemag.org/content/365/6451/eaat9351
Y. Wang and L.V. Hooper. Immune control of the microbiota prevents obesity. Science. Vol. 365, July 26, 2019, p. 316. https://science.sciencemag.org/content/365/6451/316...
https://www.sciencenews.org/article/immune-system-defects-seem-contribute-obesit...
48margd
The Fundamental Link Between Body Weight and the Immune System
James Hamblin | Aug 2, 2019
Inflammation plays a critical role in determining how we digest food, and it’s only now starting to reveal itself.
...it is becoming clear that some people’s guts are simply more efficient than others’ at extracting calories from food.
...As the usage of animal antibiotics exploded in the 20th century, so too did usage in humans. The rise coincides with the obesity epidemic.
...even subtle changes in the functioning of the immune system could influence microbial populations—and, hence, weight gain and metabolism.
...Because leanness and obesity seem to be transmissible through the microbiome, “metabolic disease turns out to be, in some ways, like an infectious disease,” says Lora Hooper, the chair of the immunology department at the University of Texas Southwestern Medical Center.
...on the balance, diet is the strongest contributor to gut microbiome composition
...The very ideas of “nutritional value” and “calorie content” of food seem to vary based on the microbial population of the person eating it and, potentially, her immune status. A person’s own microbes—and those contained in any given food—would have to be considered as another component of the already flimsy calories-in, calories-out equation. This would also compound the challenges already facing nutrition labels.
...“A lot of the recent research on probiotics suggests it’s really not easy to keep and sustain new communities,” (Zac Stephens, a microbial ecologist at the University of Utah) says. The immune system could explain that. “It may well be that your immune response gets ‘stuck’ at an early age based on what you’ve exposed it to. Probiotics might not be enough to change a person’s microbiome, because your immune system determined early on that certain microbes are either appropriate or inappropriate in your gut.”
Stephens says the relationship between weight and the immune system is likely to get more complicated before it gets simpler. That makes it difficult to give concrete advice. “Keeping diverse gut microbes with diverse dietary sources is probably the safest advice for now,” he says. “That will stimulate a healthy, strong immune system that can learn and regulate and do all the things it does, in ways we’re just beginning to understand.”
If all this uncertainty makes nutrition guidelines and nutrition even more inscrutable, it also stands to do some good by undermining the moralizing and simplistic character judgments often associated with body weight. Seeing obesity as a manifestation of the interplay between many systems—genetic, microbial, environmental—invites the understanding that human physiology has changed along with our relationship to the species in and around us. As these new scientific models unfold, they impugn the idea of weight as an individual character flaw, revealing it for the self-destructive myth it has always been.
https://www.theatlantic.com/health/archive/2019/08/inflammations-immune-system-o...
-------------------------------------------------------------------------------------------------
...the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia and inflammatory markers in diet-induced obese mice...
Patrice D. Cani. 2019. Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome (Microbes4U). ClinicalTrials.gov Identifier: NCT02637115. First Posted : December 22, 2015. Last Update Posted : May 17, 2019. https://clinicaltrials.gov/ct2/show/NCT02637115
Brief Summary:
Overweight and obesity have reached worldwide epidemic level. Both overweight and obesity are characterized by comorbidities such as cardio-metabolic risk factors (i.e., insulin resistance, type 2 diabetes, hypertension, dyslipidemia, low-grade inflammation) representing a major public health problem. Therefore, it is urgent to find a therapeutic solution to target all these metabolic disorders. Among the environmental factors able to influence the individual susceptibility to gain weight and to develop metabolic disorders associated with obesity, more and more evidence show that the trillions of bacteria housed in our gastro-intestinal tract (i.e, gut microbiota) influence host metabolism. The investigators recently discovered a putative interesting microbial candidate, namely Akkermansia muciniphila (Akk). More exactly, we found that the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia and inflammatory markers in diet-induced obese mice. Moreover, in overweight/obese patients with cardiovascular risk factors subjected to a calorie restriction diet (calorie restriction diet for 6 weeks and an additional 6 weeks of weight maintenance), a higher abundance of Akkermansia muciniphila was associated with a better cardio-metabolic status in these patients. The investigators also discovered that patients having more Akkermansia muciniphila in their gut before the calorie restriction exhibited a greater improvement in glucose homoeostasis, blood lipids and body composition after calorie restriction. These observations suggested that the administration of Akkermansia muciniphila in overweight or obese people could be a very interesting therapeutic solution. Currently, no human study has investigated the beneficial effects of Akkermansia muciniphila administration on obesity and metabolic disorders. The overall objective of this study is to evaluate the effects associated with the administration of live or heat-killed Akkermansia muciniphila on the metabolic disorders (insulin-resistance, type-2 diabetes, dyslipidemia, inflammation) related to overweight and obesity in humans.
James Hamblin | Aug 2, 2019
Inflammation plays a critical role in determining how we digest food, and it’s only now starting to reveal itself.
...it is becoming clear that some people’s guts are simply more efficient than others’ at extracting calories from food.
...As the usage of animal antibiotics exploded in the 20th century, so too did usage in humans. The rise coincides with the obesity epidemic.
...even subtle changes in the functioning of the immune system could influence microbial populations—and, hence, weight gain and metabolism.
...Because leanness and obesity seem to be transmissible through the microbiome, “metabolic disease turns out to be, in some ways, like an infectious disease,” says Lora Hooper, the chair of the immunology department at the University of Texas Southwestern Medical Center.
...on the balance, diet is the strongest contributor to gut microbiome composition
...The very ideas of “nutritional value” and “calorie content” of food seem to vary based on the microbial population of the person eating it and, potentially, her immune status. A person’s own microbes—and those contained in any given food—would have to be considered as another component of the already flimsy calories-in, calories-out equation. This would also compound the challenges already facing nutrition labels.
...“A lot of the recent research on probiotics suggests it’s really not easy to keep and sustain new communities,” (Zac Stephens, a microbial ecologist at the University of Utah) says. The immune system could explain that. “It may well be that your immune response gets ‘stuck’ at an early age based on what you’ve exposed it to. Probiotics might not be enough to change a person’s microbiome, because your immune system determined early on that certain microbes are either appropriate or inappropriate in your gut.”
Stephens says the relationship between weight and the immune system is likely to get more complicated before it gets simpler. That makes it difficult to give concrete advice. “Keeping diverse gut microbes with diverse dietary sources is probably the safest advice for now,” he says. “That will stimulate a healthy, strong immune system that can learn and regulate and do all the things it does, in ways we’re just beginning to understand.”
If all this uncertainty makes nutrition guidelines and nutrition even more inscrutable, it also stands to do some good by undermining the moralizing and simplistic character judgments often associated with body weight. Seeing obesity as a manifestation of the interplay between many systems—genetic, microbial, environmental—invites the understanding that human physiology has changed along with our relationship to the species in and around us. As these new scientific models unfold, they impugn the idea of weight as an individual character flaw, revealing it for the self-destructive myth it has always been.
https://www.theatlantic.com/health/archive/2019/08/inflammations-immune-system-o...
-------------------------------------------------------------------------------------------------
...the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia and inflammatory markers in diet-induced obese mice...
Patrice D. Cani. 2019. Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome (Microbes4U). ClinicalTrials.gov Identifier: NCT02637115. First Posted : December 22, 2015. Last Update Posted : May 17, 2019. https://clinicaltrials.gov/ct2/show/NCT02637115
Brief Summary:
Overweight and obesity have reached worldwide epidemic level. Both overweight and obesity are characterized by comorbidities such as cardio-metabolic risk factors (i.e., insulin resistance, type 2 diabetes, hypertension, dyslipidemia, low-grade inflammation) representing a major public health problem. Therefore, it is urgent to find a therapeutic solution to target all these metabolic disorders. Among the environmental factors able to influence the individual susceptibility to gain weight and to develop metabolic disorders associated with obesity, more and more evidence show that the trillions of bacteria housed in our gastro-intestinal tract (i.e, gut microbiota) influence host metabolism. The investigators recently discovered a putative interesting microbial candidate, namely Akkermansia muciniphila (Akk). More exactly, we found that the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia and inflammatory markers in diet-induced obese mice. Moreover, in overweight/obese patients with cardiovascular risk factors subjected to a calorie restriction diet (calorie restriction diet for 6 weeks and an additional 6 weeks of weight maintenance), a higher abundance of Akkermansia muciniphila was associated with a better cardio-metabolic status in these patients. The investigators also discovered that patients having more Akkermansia muciniphila in their gut before the calorie restriction exhibited a greater improvement in glucose homoeostasis, blood lipids and body composition after calorie restriction. These observations suggested that the administration of Akkermansia muciniphila in overweight or obese people could be a very interesting therapeutic solution. Currently, no human study has investigated the beneficial effects of Akkermansia muciniphila administration on obesity and metabolic disorders. The overall objective of this study is to evaluate the effects associated with the administration of live or heat-killed Akkermansia muciniphila on the metabolic disorders (insulin-resistance, type-2 diabetes, dyslipidemia, inflammation) related to overweight and obesity in humans.
492wonderY
>48 margd: Thanks for keeping this thread going. That Atlantic article is quite interesting and thought provoking.
50margd
Millennials, Gen Y need to eat less, workout more to stave off obesity: York U study
September 21, 2015
If you are struggling with weight gain, you might be surprised to know that your parents had it easier – they could eat more and exercise less, and still avoid obesity, according to a recent study out of York University’s Faculty of Health.
...Professor Jennifer Kuk in the School of Kinesiology and Health Science...explains that our body weight is impacted by our lifestyle and environment, such as medication use, environmental pollutants, genetics, timing of food intake, stress, gut bacteria and even nighttime light exposure. “Ultimately, maintaining a healthy body weight is now more challenging than ever.”...
http://news.yorku.ca/2015/09/21/millennials-gen-y-need-to-eat-less-workout-more-...
----------------------------------------------------------------------------------------------------------
Ruth E.Brown et al. 2016. Secular differences in the association between caloric intake, macronutrient intake, and physical activity with obesity. Obesity Research & Clinical Practice. Volume 10, Issue 3, May–June 2016, Pages 243-255. https://doi.org/10.1016/j.orcp.2015.08.007
Summary
Background
To determine whether the relationship between caloric intake, macronutrient intake, and physical activity with obesity has changed over time.
Methods
Dietary data from 36,377 U.S. adults from the National Health and Nutrition Survey (NHANES) between 1971 and 2008 was used. Physical activity frequency data was only available in 14,419 adults between 1988 and 2006. Generalised linear models were used to examine if the association between total caloric intake, percent dietary macronutrient intake and physical activity with body mass index (BMI) was different over time.
Results
Between 1971 and 2008, BMI, total caloric intake and carbohydrate intake increased 10–14%, and fat and protein intake decreased 5–9%. Between 1988 and 2006, frequency of leisure time physical activity increased 47–120%. However, for a given amount of caloric intake, macronutrient intake or leisure time physical activity, the predicted BMI was up to 2.3 kg/m2 higher in 2006 that in 1988 in the mutually adjusted model (P
September 21, 2015
If you are struggling with weight gain, you might be surprised to know that your parents had it easier – they could eat more and exercise less, and still avoid obesity, according to a recent study out of York University’s Faculty of Health.
...Professor Jennifer Kuk in the School of Kinesiology and Health Science...explains that our body weight is impacted by our lifestyle and environment, such as medication use, environmental pollutants, genetics, timing of food intake, stress, gut bacteria and even nighttime light exposure. “Ultimately, maintaining a healthy body weight is now more challenging than ever.”...
http://news.yorku.ca/2015/09/21/millennials-gen-y-need-to-eat-less-workout-more-...
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Ruth E.Brown et al. 2016. Secular differences in the association between caloric intake, macronutrient intake, and physical activity with obesity. Obesity Research & Clinical Practice. Volume 10, Issue 3, May–June 2016, Pages 243-255. https://doi.org/10.1016/j.orcp.2015.08.007
Summary
Background
To determine whether the relationship between caloric intake, macronutrient intake, and physical activity with obesity has changed over time.
Methods
Dietary data from 36,377 U.S. adults from the National Health and Nutrition Survey (NHANES) between 1971 and 2008 was used. Physical activity frequency data was only available in 14,419 adults between 1988 and 2006. Generalised linear models were used to examine if the association between total caloric intake, percent dietary macronutrient intake and physical activity with body mass index (BMI) was different over time.
Results
Between 1971 and 2008, BMI, total caloric intake and carbohydrate intake increased 10–14%, and fat and protein intake decreased 5–9%. Between 1988 and 2006, frequency of leisure time physical activity increased 47–120%. However, for a given amount of caloric intake, macronutrient intake or leisure time physical activity, the predicted BMI was up to 2.3 kg/m2 higher in 2006 that in 1988 in the mutually adjusted model (P
51margd
Molecule links weight gain to gut bacteria
UT Southwestern Medical Center | September 27, 2019
Good bacteria that live in the guts of mammals program the metabolic rhythms that govern the body's absorption of dietary fat.
...the commensal, or good, bacteria that live in the guts of mammals program the metabolic rhythms that govern the body's absorption of dietary fat. Dr. Hooper, Chair of Immunology and a Howard Hughes Medical Institute Investigator, is senior author of the study.
The study also found that microbes program these so-called circadian rhythms by activating a protein named histone deacetylase 3 (HDAC3), which is made by cells that line the gut. Those cells act as intermediaries between bacteria that aid in digestion of food and proteins that enable absorption of nutrients.
..."Our results suggest that the microbiome and the circadian clock have evolved to work together to regulate metabolism...This regulatory interaction probably didn't evolve to make us obese, but when combined with today's calorie-rich diets, obesity arises"...
"Our results also suggest that disrupting the interactions between the microbiota and the body's clock could make us more likely to become obese. These disruptions happen frequently in modern life when we take antibiotics, work overnight shifts, or travel internationally. But we think that our findings might eventually lead to new treatments for obesity -- and possibly malnutrition -- by altering the bacteria in our guts."
www.sciencedaily.com/releases/2019/09/190927135200.htm
-----------------------------------------------------------------------------------
Zheng Kuang, Yuhao Wang, Yun Li, Cunqi Ye, Kelly A. Ruhn, Cassie L. Behrendt, Eric N. Olson, Lora V. Hooper. The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science, 2019; 365 (6460): 1428 DOI: 10.1126/science.aaw3134 https://science.sciencemag.org/content/365/6460/1428
Microbial entrainment of metabolism
The metabolism of mammals is synchronized to daily cycles relating to sleep and mealtimes. It is not surprising that the gut microbiota, which aids in digestion, should also display daily cycling. Kuang et al. found that the gut microbiota can mediate daily cycles epigenetically (see the Perspective by Bishehsari and Keshavarzian). The microbiota induces rhythmic expression of histone deacetylase 3 (HDAC3) in epithelial cells of the small intestine, but not those of the colon. HDAC3 expression drives oscillations in intestinal metabolic gene expression, especially for nutrient transport and lipid metabolism. HDAC3 also directly activates estrogen-related receptor α, which promotes lipid absorption. Consequently, mice that lack a gut microbiota lack daily regulation of their metabolism and become obese on high-fat chow. Disruption of HDAC3 cycling could be an explanation for human obesity associated with antibiotic damage to the microbiota and with sleep disruption caused by jet lag and nighttime working.
Abstract
Circadian rhythmicity is a defining feature of mammalian metabolism that synchronizes metabolic processes to day-night light cycles. Here, we show that the intestinal microbiota programs diurnal metabolic rhythms in the mouse small intestine through histone deacetylase 3 (HDAC3). The microbiota induced expression of intestinal epithelial HDAC3, which was recruited rhythmically to chromatin, and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned noncanonically to coactivate estrogen-related receptor α, inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues for regulation of diurnal metabolic rhythms and pinpoint a key mechanism by which the microbiota controls host metabolism.
UT Southwestern Medical Center | September 27, 2019
Good bacteria that live in the guts of mammals program the metabolic rhythms that govern the body's absorption of dietary fat.
...the commensal, or good, bacteria that live in the guts of mammals program the metabolic rhythms that govern the body's absorption of dietary fat. Dr. Hooper, Chair of Immunology and a Howard Hughes Medical Institute Investigator, is senior author of the study.
The study also found that microbes program these so-called circadian rhythms by activating a protein named histone deacetylase 3 (HDAC3), which is made by cells that line the gut. Those cells act as intermediaries between bacteria that aid in digestion of food and proteins that enable absorption of nutrients.
..."Our results suggest that the microbiome and the circadian clock have evolved to work together to regulate metabolism...This regulatory interaction probably didn't evolve to make us obese, but when combined with today's calorie-rich diets, obesity arises"...
"Our results also suggest that disrupting the interactions between the microbiota and the body's clock could make us more likely to become obese. These disruptions happen frequently in modern life when we take antibiotics, work overnight shifts, or travel internationally. But we think that our findings might eventually lead to new treatments for obesity -- and possibly malnutrition -- by altering the bacteria in our guts."
www.sciencedaily.com/releases/2019/09/190927135200.htm
-----------------------------------------------------------------------------------
Zheng Kuang, Yuhao Wang, Yun Li, Cunqi Ye, Kelly A. Ruhn, Cassie L. Behrendt, Eric N. Olson, Lora V. Hooper. The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science, 2019; 365 (6460): 1428 DOI: 10.1126/science.aaw3134 https://science.sciencemag.org/content/365/6460/1428
Microbial entrainment of metabolism
The metabolism of mammals is synchronized to daily cycles relating to sleep and mealtimes. It is not surprising that the gut microbiota, which aids in digestion, should also display daily cycling. Kuang et al. found that the gut microbiota can mediate daily cycles epigenetically (see the Perspective by Bishehsari and Keshavarzian). The microbiota induces rhythmic expression of histone deacetylase 3 (HDAC3) in epithelial cells of the small intestine, but not those of the colon. HDAC3 expression drives oscillations in intestinal metabolic gene expression, especially for nutrient transport and lipid metabolism. HDAC3 also directly activates estrogen-related receptor α, which promotes lipid absorption. Consequently, mice that lack a gut microbiota lack daily regulation of their metabolism and become obese on high-fat chow. Disruption of HDAC3 cycling could be an explanation for human obesity associated with antibiotic damage to the microbiota and with sleep disruption caused by jet lag and nighttime working.
Abstract
Circadian rhythmicity is a defining feature of mammalian metabolism that synchronizes metabolic processes to day-night light cycles. Here, we show that the intestinal microbiota programs diurnal metabolic rhythms in the mouse small intestine through histone deacetylase 3 (HDAC3). The microbiota induced expression of intestinal epithelial HDAC3, which was recruited rhythmically to chromatin, and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned noncanonically to coactivate estrogen-related receptor α, inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues for regulation of diurnal metabolic rhythms and pinpoint a key mechanism by which the microbiota controls host metabolism.
52margd
Simply, see video (05:26) at https://www.cell.com/cell/fulltext/S0092-8674(15)01481-6 :
https://www.cell.com/cms/10.1016/j.cell.2015.11.001/attachment/769da64f-7037-4ab...
Personalized diets may be the future of nutrition. But the science isn’t all there yet
Tina Hesman Saey | Sept 30, 2019
...Genes explain less than half of an individual’s varying responses to food
...What’s more, the macronutrient content of the food — the amount of carbs, fat and protein — accounted for only 16 to 32 percent of varying responses, the researchers found. The rest is still a mystery, and could relate to a litany of causes. Medications, the amount and quality of sleep people got, how much they exercised, when people ate and what order they ate foods in, their overall health and biological rhythms as well as the microbes living in the volunteers’ guts might all influence their reactions
...Gut microbes are probably the most important factor...play a big role in controlling how much a person’s blood sugar will spike
...But here’s where things get sticky, because what people eat also affects the microbes in the gut in very personal ways.
...“What you eat does determine which microorganisms are in your gut. There’s no question about that,” Hooper says. But exactly what about that food influences microbiome changes is a mystery.
...For instance, knowing that a food was spaghetti with tomato sauce and meat told the researchers more about how the microbiome would change than knowing the carbohydrate, fat and protein content of the food did. Microbes may be more concerned with trace nutrients or chemical components of food that aren’t included on labels, Johnson says.
...For most people,...following standard nutritional advice will help them get and stay healthy....
Citations
A.J. Johnson et al. Daily sampling reveals personalized diet-microbiome associations in humans. Cell Host & Microbe. Vol. 25, June 12, 2019, p. 789. doi:10.1016/j.chom.2019.05.005. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(19)30250-1
Highlights
• Daily microbiome variation is related to food choices, but not to conventional nutrients
• Daily microbiome variation depends on at least two days of dietary history
• Similar foods have different effects on different people’s microbiomes
Summary
Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.
T. Spector et al. Predicting personal metabolic responses to food using multi-omics machine learning in over 1000 twins and singletons from the UK and US: The PREDICT 1 Study. American Society for Nutrition’s Nutrition 2019 meeting, Baltimore, June 11, 2019. https://www.eventscribe.com/2019/ASN/fsPopup.asp https://www.eventscribe.com/2019/ASN/fsPopup.asp
Objectives :
Glycemic, insulinemic and lipemic postprandial responses are multi-factorial and contribute to diabetes, obesity and cardiovascular disease. The aim of the PREDICT I study is to assess the genetic, metabolic, metagenomic, and meal-context contribution to postprandial responses, integrating the metabolic burden and gut microbiome to predict individual responses to food using a machine learning algorithm.
Methods :
A multi-center dietary intervention study of 1000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from the US, assessed postprandial (0-6h) metabolic responses to sequential mixed-nutrient dietary challenges in the clinic. Baseline data included metabolomics, genomics, gut metagenomics and DXA body composition. Glycemic responses to 5 duplicate isocaloric meals of different macronutrient content and self-selected meals ( more than 100,000), were tested at home using a continuous glucose monitor (CGM). Interim analysis of the genetic contributions was performed in 110 identical and 25 non-identical twin pairs.
Results :
Inter-individual variability in postprandial metabolic responses (glucose, insulin and triacylglycerol (TG)) was high in the clinic setting:... A predictive algorithm was developed and interim analyses, using at home CGM data, found that 46% of overall variation in glycemic responses could be predicted from meal content, meal context and individual baseline characteristics excluding genetic and microbiome factors. Only 29% of variation could be explained by the macronutrient content of the meal.
Conclusions :
This is the most comprehensive postprandial study performed to date. The large and modifiable variation in metabolic responses to identical meals in healthy people explains why ‘one size fits all’ nutritional guidelines are problematic. By collecting information on glucose responses to >100 margd:,000 meals we will have excellent power to use machine learning to optimise and predict individual responses to foods.
H. Mendes-Soares et al. Assessment of a personalized approach to predicting postprandial glycemic responses to food among individuals without diabetes. JAMA Network Open. Vol. 2, February 8, 2019. doi:10.1001/jamanetworkopen.2018.8102. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2723644
Abstract
Importance
Emerging evidence suggests that postprandial glycemic responses (PPGRs) to food may be influenced by and predicted according to characteristics unique to each individual, including anthropometric and microbiome variables. Interindividual diversity in PPGRs to food requires a personalized approach for the maintenance of healthy glycemic levels.
Objectives
To describe and predict the glycemic responses of individuals to a diverse array of foods using a model that considers the physiology and microbiome of the individual in addition to the characteristics of the foods consumed.
Design, Setting, and Participants
This cohort study using a personalized predictive model enrolled 327 individuals without diabetes from October 11, 2016, to December 13, 2017, in Minnesota and Florida to be part of a study lasting 6 days. The study measured anthropometric variables, described the gut microbial composition, and assessed blood glucose levels every 5 minutes using a continuous glucose monitor. Participants logged their food and activity information for the duration of the study. A predictive model of individualized PPGRs to a diverse array of foods was trained and applied.
Main Outcomes and Measures
Glycemic responses to food consumed over 6 days for each participant. The predictive model of personalized PPGRs considered individual features, including the microbiome, in addition to the features of the foods consumed.
Results
Postprandial response to the same foods varied across 327 individuals (mean SD age, 45 12 years; 78.0% female). A model predicting each individual’s responses to food that considers several individual factors in addition to food features had better overall performance (R = 0.62) than current standard-of-care approaches using nutritional content alone (R = 0.34 for calories and R = 0.40 for carbohydrates) to control postprandial glycemic levels.
Conclusions and Relevance
Across the cohort of adults without diabetes who were examined, a personalized predictive model that considers unique features of the individual, such as clinical characteristics, physiological variables, and the microbiome, in addition to nutrient content was more predictive than current dietary approaches that focus only on the calorie or carbohydrate content of foods. Providing individuals with tools to manage their glycemic responses to food based on personalized predictions of their PPGRs may allow them to maintain their blood glucose levels within limits associated with good health.
D. Zeevi et al. Personalized nutrition by prediction of glycemic responses. Cell. Vol. 163, November 19, 2015, p. 1079. doi:10.1016/j.cell.2015.11.001.
https://www.cell.com/cell/fulltext/S0092-8674(15)01481-6
Highlights
• High interpersonal variability in post-meal glucose observed in an 800-person cohort
• Using personal and microbiome features enables accurate glucose response prediction
• Prediction is accurate and superior to common practice in an independent cohort
• Short-term personalized dietary interventions successfully lower post-meal glucose
Summary
Elevated postprandial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes, but existing dietary methods for controlling them have limited efficacy. Here, we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals. We validated these predictions in an independent 100-person cohort. Finally, a blinded randomized controlled dietary intervention based on this algorithm resulted in significantly lower postprandial responses and consistent alterations to gut microbiota configuration. Together, our results suggest that personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences.
https://www.sciencenews.org/article/personalized-diets-may-be-future-nutrition-b...
https://www.cell.com/cms/10.1016/j.cell.2015.11.001/attachment/769da64f-7037-4ab...
Personalized diets may be the future of nutrition. But the science isn’t all there yet
Tina Hesman Saey | Sept 30, 2019
...Genes explain less than half of an individual’s varying responses to food
...What’s more, the macronutrient content of the food — the amount of carbs, fat and protein — accounted for only 16 to 32 percent of varying responses, the researchers found. The rest is still a mystery, and could relate to a litany of causes. Medications, the amount and quality of sleep people got, how much they exercised, when people ate and what order they ate foods in, their overall health and biological rhythms as well as the microbes living in the volunteers’ guts might all influence their reactions
...Gut microbes are probably the most important factor...play a big role in controlling how much a person’s blood sugar will spike
...But here’s where things get sticky, because what people eat also affects the microbes in the gut in very personal ways.
...“What you eat does determine which microorganisms are in your gut. There’s no question about that,” Hooper says. But exactly what about that food influences microbiome changes is a mystery.
...For instance, knowing that a food was spaghetti with tomato sauce and meat told the researchers more about how the microbiome would change than knowing the carbohydrate, fat and protein content of the food did. Microbes may be more concerned with trace nutrients or chemical components of food that aren’t included on labels, Johnson says.
...For most people,...following standard nutritional advice will help them get and stay healthy....
Citations
A.J. Johnson et al. Daily sampling reveals personalized diet-microbiome associations in humans. Cell Host & Microbe. Vol. 25, June 12, 2019, p. 789. doi:10.1016/j.chom.2019.05.005. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(19)30250-1
Highlights
• Daily microbiome variation is related to food choices, but not to conventional nutrients
• Daily microbiome variation depends on at least two days of dietary history
• Similar foods have different effects on different people’s microbiomes
Summary
Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.
T. Spector et al. Predicting personal metabolic responses to food using multi-omics machine learning in over 1000 twins and singletons from the UK and US: The PREDICT 1 Study. American Society for Nutrition’s Nutrition 2019 meeting, Baltimore, June 11, 2019. https://www.eventscribe.com/2019/ASN/fsPopup.asp https://www.eventscribe.com/2019/ASN/fsPopup.asp
Objectives :
Glycemic, insulinemic and lipemic postprandial responses are multi-factorial and contribute to diabetes, obesity and cardiovascular disease. The aim of the PREDICT I study is to assess the genetic, metabolic, metagenomic, and meal-context contribution to postprandial responses, integrating the metabolic burden and gut microbiome to predict individual responses to food using a machine learning algorithm.
Methods :
A multi-center dietary intervention study of 1000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from the US, assessed postprandial (0-6h) metabolic responses to sequential mixed-nutrient dietary challenges in the clinic. Baseline data included metabolomics, genomics, gut metagenomics and DXA body composition. Glycemic responses to 5 duplicate isocaloric meals of different macronutrient content and self-selected meals ( more than 100,000), were tested at home using a continuous glucose monitor (CGM). Interim analysis of the genetic contributions was performed in 110 identical and 25 non-identical twin pairs.
Results :
Inter-individual variability in postprandial metabolic responses (glucose, insulin and triacylglycerol (TG)) was high in the clinic setting:... A predictive algorithm was developed and interim analyses, using at home CGM data, found that 46% of overall variation in glycemic responses could be predicted from meal content, meal context and individual baseline characteristics excluding genetic and microbiome factors. Only 29% of variation could be explained by the macronutrient content of the meal.
Conclusions :
This is the most comprehensive postprandial study performed to date. The large and modifiable variation in metabolic responses to identical meals in healthy people explains why ‘one size fits all’ nutritional guidelines are problematic. By collecting information on glucose responses to >100 margd:,000 meals we will have excellent power to use machine learning to optimise and predict individual responses to foods.
H. Mendes-Soares et al. Assessment of a personalized approach to predicting postprandial glycemic responses to food among individuals without diabetes. JAMA Network Open. Vol. 2, February 8, 2019. doi:10.1001/jamanetworkopen.2018.8102. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2723644
Abstract
Importance
Emerging evidence suggests that postprandial glycemic responses (PPGRs) to food may be influenced by and predicted according to characteristics unique to each individual, including anthropometric and microbiome variables. Interindividual diversity in PPGRs to food requires a personalized approach for the maintenance of healthy glycemic levels.
Objectives
To describe and predict the glycemic responses of individuals to a diverse array of foods using a model that considers the physiology and microbiome of the individual in addition to the characteristics of the foods consumed.
Design, Setting, and Participants
This cohort study using a personalized predictive model enrolled 327 individuals without diabetes from October 11, 2016, to December 13, 2017, in Minnesota and Florida to be part of a study lasting 6 days. The study measured anthropometric variables, described the gut microbial composition, and assessed blood glucose levels every 5 minutes using a continuous glucose monitor. Participants logged their food and activity information for the duration of the study. A predictive model of individualized PPGRs to a diverse array of foods was trained and applied.
Main Outcomes and Measures
Glycemic responses to food consumed over 6 days for each participant. The predictive model of personalized PPGRs considered individual features, including the microbiome, in addition to the features of the foods consumed.
Results
Postprandial response to the same foods varied across 327 individuals (mean SD age, 45 12 years; 78.0% female). A model predicting each individual’s responses to food that considers several individual factors in addition to food features had better overall performance (R = 0.62) than current standard-of-care approaches using nutritional content alone (R = 0.34 for calories and R = 0.40 for carbohydrates) to control postprandial glycemic levels.
Conclusions and Relevance
Across the cohort of adults without diabetes who were examined, a personalized predictive model that considers unique features of the individual, such as clinical characteristics, physiological variables, and the microbiome, in addition to nutrient content was more predictive than current dietary approaches that focus only on the calorie or carbohydrate content of foods. Providing individuals with tools to manage their glycemic responses to food based on personalized predictions of their PPGRs may allow them to maintain their blood glucose levels within limits associated with good health.
D. Zeevi et al. Personalized nutrition by prediction of glycemic responses. Cell. Vol. 163, November 19, 2015, p. 1079. doi:10.1016/j.cell.2015.11.001.
https://www.cell.com/cell/fulltext/S0092-8674(15)01481-6
Highlights
• High interpersonal variability in post-meal glucose observed in an 800-person cohort
• Using personal and microbiome features enables accurate glucose response prediction
• Prediction is accurate and superior to common practice in an independent cohort
• Short-term personalized dietary interventions successfully lower post-meal glucose
Summary
Elevated postprandial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes, but existing dietary methods for controlling them have limited efficacy. Here, we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals. We validated these predictions in an independent 100-person cohort. Finally, a blinded randomized controlled dietary intervention based on this algorithm resulted in significantly lower postprandial responses and consistent alterations to gut microbiota configuration. Together, our results suggest that personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences.
https://www.sciencenews.org/article/personalized-diets-may-be-future-nutrition-b...
53margd
Is this how fructose worsens the effect of high fat diets?
Catharine Paddock | 5 October 2019
..."Fructose makes the liver accumulate fat," says senior study author C. Ronald Kahn, a professor of medicine at Harvard Medical School in Boston, MA. "It acts almost like adding more fat to the diet," he continues.
"This contrasts the effect of adding more glucose to the diet, which promotes the liver's ability to burn fat, and, therefore, actually makes for a healthier metabolism," he adds.
....Added sugar in the diet has two forms: sucrose or high fructose corn syrup. Both these forms contain fructose and glucose.
...mice on the regular diet with fructose or glucose in their drinking water gained around 30% more weight than mice that drank plain water. Also, these mice did not develop high blood glucose, a feature of diabetes.
All three groups of mice on the high fat diets did develop obesity, with increases in body weight of 40–60% on average. In addition, these mice showed signs of liver enlargement and hepatic steatosis, or fat buildup in the liver.
The high fat diet mice on regular water and water with added fructose also developed insulin resistance and high blood sugar, and their insulin levels doubled.
However, while the high fat diet mice on water with added glucose gained a similar amount of weight as their other high fat diet companions, they did not develop the other symptoms, despite having the same calorie intakes.
...The mice on high fat diets with high fructose had the highest levels of acylcarnitines (byproducts of fat burning in the liver). However, the mice on high fat diets with high glucose had lower levels of these high liver fat markers than the high fat diet mice on plain water.
...suggest(s) that glucose helps the liver to burn fat.
In contrast to acylcarnitines, higher levels of (carnitine palmitoyltransferase 1A (CPT1A), a mitochondrial enzyme with a key role in fat burning) are a good sign as they indicate that the mitochondria are carrying out their fat burning function.
The high fat mice on water with added fructose, however, had low levels and lower activity of CPT1A. This observation suggested that something was wrong with the mitochondria in their liver cells.
...When the team examined the liver cells of the high fat plus fructose mice, the scientists found that the mitochondria were fragmented (not nice ovoid shape and crosshatching), suggesting that they were not burning fat very well. In contrast, the mitochondria of the high fat plus glucose mice were a healthy shape...
https://www.medicalnewstoday.com/articles/326550.php
______________________________________________________________________
Samir Softic et al. 2019. Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins. Cell Metabolism. Volume 30, ISSUE 4, P735-753.e4, October 01, 2019. DOI:https://doi.org/10.1016/j.cmet.2019.09.003
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30504-2
Highlights
• Addition of fructose to a high-fat diet increases hepatic malonyl-CoA more than glucose
• Knockdown of the fructose metabolizing gene ketohexokinase increases CTP1a levels
• Fructose supplementation alters mitochondrial size and function
• Dietary fructose induces acetylation of ACADL and CPT1a to modify fat oxidation
Summary
Dietary sugars, fructose and glucose, promote hepatic de novo lipogenesis and modify the effects of a high-fat diet (HFD) on the development of insulin resistance. Here, we show that fructose and glucose supplementation of an HFD exert divergent effects on hepatic mitochondrial function and fatty acid oxidation. This is mediated via three different nodes of regulation, including differential effects on malonyl-CoA levels, effects on mitochondrial size/protein abundance, and acetylation of mitochondrial proteins. HFD- and HFD plus fructose-fed mice have decreased CTP1a activity, the rate-limiting enzyme of fatty acid oxidation, whereas knockdown of fructose metabolism increases CPT1a and its acylcarnitine products. Furthermore, fructose-supplemented HFD leads to increased acetylation of ACADL and CPT1a, which is associated with decreased fat metabolism. In summary, dietary fructose, but not glucose, supplementation of HFD impairs mitochondrial size, function, and protein acetylation, resulting in decreased fatty acid oxidation and development of metabolic dysregulation.
Catharine Paddock | 5 October 2019
..."Fructose makes the liver accumulate fat," says senior study author C. Ronald Kahn, a professor of medicine at Harvard Medical School in Boston, MA. "It acts almost like adding more fat to the diet," he continues.
"This contrasts the effect of adding more glucose to the diet, which promotes the liver's ability to burn fat, and, therefore, actually makes for a healthier metabolism," he adds.
....Added sugar in the diet has two forms: sucrose or high fructose corn syrup. Both these forms contain fructose and glucose.
...mice on the regular diet with fructose or glucose in their drinking water gained around 30% more weight than mice that drank plain water. Also, these mice did not develop high blood glucose, a feature of diabetes.
All three groups of mice on the high fat diets did develop obesity, with increases in body weight of 40–60% on average. In addition, these mice showed signs of liver enlargement and hepatic steatosis, or fat buildup in the liver.
The high fat diet mice on regular water and water with added fructose also developed insulin resistance and high blood sugar, and their insulin levels doubled.
However, while the high fat diet mice on water with added glucose gained a similar amount of weight as their other high fat diet companions, they did not develop the other symptoms, despite having the same calorie intakes.
...The mice on high fat diets with high fructose had the highest levels of acylcarnitines (byproducts of fat burning in the liver). However, the mice on high fat diets with high glucose had lower levels of these high liver fat markers than the high fat diet mice on plain water.
...suggest(s) that glucose helps the liver to burn fat.
In contrast to acylcarnitines, higher levels of (carnitine palmitoyltransferase 1A (CPT1A), a mitochondrial enzyme with a key role in fat burning) are a good sign as they indicate that the mitochondria are carrying out their fat burning function.
The high fat mice on water with added fructose, however, had low levels and lower activity of CPT1A. This observation suggested that something was wrong with the mitochondria in their liver cells.
...When the team examined the liver cells of the high fat plus fructose mice, the scientists found that the mitochondria were fragmented (not nice ovoid shape and crosshatching), suggesting that they were not burning fat very well. In contrast, the mitochondria of the high fat plus glucose mice were a healthy shape...
https://www.medicalnewstoday.com/articles/326550.php
______________________________________________________________________
Samir Softic et al. 2019. Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins. Cell Metabolism. Volume 30, ISSUE 4, P735-753.e4, October 01, 2019. DOI:https://doi.org/10.1016/j.cmet.2019.09.003
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30504-2
Highlights
• Addition of fructose to a high-fat diet increases hepatic malonyl-CoA more than glucose
• Knockdown of the fructose metabolizing gene ketohexokinase increases CTP1a levels
• Fructose supplementation alters mitochondrial size and function
• Dietary fructose induces acetylation of ACADL and CPT1a to modify fat oxidation
Summary
Dietary sugars, fructose and glucose, promote hepatic de novo lipogenesis and modify the effects of a high-fat diet (HFD) on the development of insulin resistance. Here, we show that fructose and glucose supplementation of an HFD exert divergent effects on hepatic mitochondrial function and fatty acid oxidation. This is mediated via three different nodes of regulation, including differential effects on malonyl-CoA levels, effects on mitochondrial size/protein abundance, and acetylation of mitochondrial proteins. HFD- and HFD plus fructose-fed mice have decreased CTP1a activity, the rate-limiting enzyme of fatty acid oxidation, whereas knockdown of fructose metabolism increases CPT1a and its acylcarnitine products. Furthermore, fructose-supplemented HFD leads to increased acetylation of ACADL and CPT1a, which is associated with decreased fat metabolism. In summary, dietary fructose, but not glucose, supplementation of HFD impairs mitochondrial size, function, and protein acetylation, resulting in decreased fatty acid oxidation and development of metabolic dysregulation.
54margd
The Obesity Era
As the American people got fatter, so did marmosets, vervet monkeys and mice. The problem may be bigger than any of us.
Aeon | David Berreby | June 19, 2013
...reported in 2010 by the biostatistician David B Allison and his co-authors at the University of Alabama in Birmingham: over the past 20 years or more, as the American people were getting fatter, so were America’s marmosets. As were laboratory macaques, chimpanzees, vervet monkeys and mice, as well as domestic dogs, domestic cats, and domestic and feral rats from both rural and urban areas. In fact, the researchers examined records on those eight species and found that average weight for every one had increased. The marmosets gained an average of nine per cent per decade. Lab mice gained about 11 per cent per decade. Chimps, for some reason, are doing especially badly: their average body weight had risen 35 per cent per decade. Allison, who had been hearing about an unexplained rise in the average weight of lab animals, was nonetheless surprised by the consistency across so many species. ‘Virtually in every population of animals we looked at, that met our criteria, there was the same upward trend,’ he told me.
It isn’t hard to imagine that people who are eating more themselves are giving more to their spoiled pets, or leaving sweeter, fattier garbage for street cats and rodents. But such results don’t explain why the weight gain is also occurring in species that human beings don’t pamper, such as animals in labs, whose diets are strictly controlled. In fact, lab animals’ lives are so precisely watched and measured that the researchers can rule out accidental human influence: records show those creatures gained weight over decades without any significant change in their diet or activities. Obviously, if animals are getting heavier along with us, it can’t just be that they’re eating more Snickers bars and driving to work most days. On the contrary, the trend suggests some widely shared cause, beyond the control of individuals, which is contributing to obesity across many species.
... ‘things that alter the body’s fat metabolism’ is a much wider category than food. Sleeplessness and stress...Viruses, bacteria and industrial chemicals...electric light, heat and air conditioning...the line of reasoning is not that stress causes you to eat more, but rather that it causes you to gain weight by directly altering the activities of your cells.
...We are increasingly understanding that attributing obesity to personal responsibility is very simplistic
This is the theme of perhaps the most epic of the alternative theories of obesity, put forward by Jonathan C K Wells (professor of child nutrition at University College London). As I understand his view, obesity is like poverty, or financial booms and busts, or war — a large-scale development that no one deliberately intends, but which emerges out of the millions of separate acts that together make human history...Its root cause, he proposed last year in the American Journal of Human Biology, is nothing less than the history of capitalism...
https://getpocket.com/explore/item/the-obesity-era
As the American people got fatter, so did marmosets, vervet monkeys and mice. The problem may be bigger than any of us.
Aeon | David Berreby | June 19, 2013
...reported in 2010 by the biostatistician David B Allison and his co-authors at the University of Alabama in Birmingham: over the past 20 years or more, as the American people were getting fatter, so were America’s marmosets. As were laboratory macaques, chimpanzees, vervet monkeys and mice, as well as domestic dogs, domestic cats, and domestic and feral rats from both rural and urban areas. In fact, the researchers examined records on those eight species and found that average weight for every one had increased. The marmosets gained an average of nine per cent per decade. Lab mice gained about 11 per cent per decade. Chimps, for some reason, are doing especially badly: their average body weight had risen 35 per cent per decade. Allison, who had been hearing about an unexplained rise in the average weight of lab animals, was nonetheless surprised by the consistency across so many species. ‘Virtually in every population of animals we looked at, that met our criteria, there was the same upward trend,’ he told me.
It isn’t hard to imagine that people who are eating more themselves are giving more to their spoiled pets, or leaving sweeter, fattier garbage for street cats and rodents. But such results don’t explain why the weight gain is also occurring in species that human beings don’t pamper, such as animals in labs, whose diets are strictly controlled. In fact, lab animals’ lives are so precisely watched and measured that the researchers can rule out accidental human influence: records show those creatures gained weight over decades without any significant change in their diet or activities. Obviously, if animals are getting heavier along with us, it can’t just be that they’re eating more Snickers bars and driving to work most days. On the contrary, the trend suggests some widely shared cause, beyond the control of individuals, which is contributing to obesity across many species.
... ‘things that alter the body’s fat metabolism’ is a much wider category than food. Sleeplessness and stress...Viruses, bacteria and industrial chemicals...electric light, heat and air conditioning...the line of reasoning is not that stress causes you to eat more, but rather that it causes you to gain weight by directly altering the activities of your cells.
...We are increasingly understanding that attributing obesity to personal responsibility is very simplistic
This is the theme of perhaps the most epic of the alternative theories of obesity, put forward by Jonathan C K Wells (professor of child nutrition at University College London). As I understand his view, obesity is like poverty, or financial booms and busts, or war — a large-scale development that no one deliberately intends, but which emerges out of the millions of separate acts that together make human history...Its root cause, he proposed last year in the American Journal of Human Biology, is nothing less than the history of capitalism...
https://getpocket.com/explore/item/the-obesity-era
55margd
51 contd.
How to Increase Gut Bacterial Richness
Written By Michael Greger M.D. FACLM on October 29th, 2019
https://nutritionfacts.org/2019/10/29/how-to-increase-gut-bacterial-richness/
Gut Microbiome – Strike It Rich with Whole Grains
Michael Greger M.D. FACLM November 9th, 2016 Volume 33
https://nutritionfacts.org/video/gut-microbiome-strike-it-rich-with-whole-grains...
How to Increase Gut Bacterial Richness
Written By Michael Greger M.D. FACLM on October 29th, 2019
https://nutritionfacts.org/2019/10/29/how-to-increase-gut-bacterial-richness/
Gut Microbiome – Strike It Rich with Whole Grains
Michael Greger M.D. FACLM November 9th, 2016 Volume 33
https://nutritionfacts.org/video/gut-microbiome-strike-it-rich-with-whole-grains...
56margd
Emily L. Goldberg et al. 2019. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 15 Nov 2019:Vol. 4, Issue 41, eaav2026 DOI: 10.1126/sciimmunol.aav2026 https://immunology.sciencemag.org/content/4/41/eaav2026
Putting mice on a keto diet
Our immune responses to infections are influenced by several extrinsic factors, including weather, social interactions, and diet. Here, Goldberg et al. report that feeding mice a high-fat, low-carbohydrate ketogenic diet confers protection in the context of lethal influenza infection. By characterizing the immune response in the lungs, the authors identified that ketogenic diet promoted the expansion of γδ T cells in the lung. Using mice lacking γδ T cells, the authors have established the functional importance of these cells in conferring protection. Their findings suggest that γδ T cells improve barrier function in the lungs by modifying differentiation and function of the airway epithelial cells.
Abstract
Influenza A virus (IAV) infection–associated morbidity and mortality are a key global health care concern, necessitating the identification of new therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet because neither feeding mice a high-fat, high-carbohydrate diet nor providing chemical ketone body substrate that bypasses hepatic ketogenesis protected against infection. Therefore, KD-mediated immune-metabolic integration represents a viable avenue toward preventing or alleviating influenza disease.
Putting mice on a keto diet
Our immune responses to infections are influenced by several extrinsic factors, including weather, social interactions, and diet. Here, Goldberg et al. report that feeding mice a high-fat, low-carbohydrate ketogenic diet confers protection in the context of lethal influenza infection. By characterizing the immune response in the lungs, the authors identified that ketogenic diet promoted the expansion of γδ T cells in the lung. Using mice lacking γδ T cells, the authors have established the functional importance of these cells in conferring protection. Their findings suggest that γδ T cells improve barrier function in the lungs by modifying differentiation and function of the airway epithelial cells.
Abstract
Influenza A virus (IAV) infection–associated morbidity and mortality are a key global health care concern, necessitating the identification of new therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet because neither feeding mice a high-fat, high-carbohydrate diet nor providing chemical ketone body substrate that bypasses hepatic ketogenesis protected against infection. Therefore, KD-mediated immune-metabolic integration represents a viable avenue toward preventing or alleviating influenza disease.
58margd
In my limited experience, they are euthanized, or if suitable/needed, they are used in other studies or adopted as pets by students in the lab. My son had a much-loved mouse, but even pet mice are unfortunately short-lived.
59margd
This is why fiber, which passes through to the intestines to be digested by the microbiome, signals satiety?
Full intestines, more than full stomachs, may tell mice to stop eating
Laura Sanders | November 19, 2019
Newly described nerve endings (pink) in a mouse’s intestine sense stretching, a pull that may send a “stop eating” signal to the brain.
The results, published November 14 in Cell, could point out new ways to treat obesity, or even help explain how gastric bypass surgeries limit eating. Those procedures result in food moving faster through the stomach into the intestines, stretching the gut in a way that might signal fullness, the authors speculate.
...Different stretch-sensing cells in the stomach also curbed mice’s appetites, but to a lesser extent, the researchers found.
These nerve cell endings relay messages up the vagus nerve (SN: 11/13/15), which then zips signals to the brain. These messages about intestinal stretching help influence the eat-or-not decision, researchers suspect.
https://www.sciencenews.org/article/full-intestines-more-than-full-stomachs-may-...
Bai L, Mesgarzadeh S, Ramesh KS, Huey EL, Liu Y, Gray LA, Aitken TJ, Chen Y, Beutler LR, Ahn JS, Madisen L, Zeng H, Krasnow MA, Knight ZA. Genetic Identification of Vagal Sensory Neurons That Control Feeding. Cell. 2019 Nov 14; 179(5):1129-1143.e23. PMID: 31730854. https://www.ncbi.nlm.nih.gov
Full intestines, more than full stomachs, may tell mice to stop eating
Laura Sanders | November 19, 2019
Newly described nerve endings (pink) in a mouse’s intestine sense stretching, a pull that may send a “stop eating” signal to the brain.
The results, published November 14 in Cell, could point out new ways to treat obesity, or even help explain how gastric bypass surgeries limit eating. Those procedures result in food moving faster through the stomach into the intestines, stretching the gut in a way that might signal fullness, the authors speculate.
...Different stretch-sensing cells in the stomach also curbed mice’s appetites, but to a lesser extent, the researchers found.
These nerve cell endings relay messages up the vagus nerve (SN: 11/13/15), which then zips signals to the brain. These messages about intestinal stretching help influence the eat-or-not decision, researchers suspect.
https://www.sciencenews.org/article/full-intestines-more-than-full-stomachs-may-...
Bai L, Mesgarzadeh S, Ramesh KS, Huey EL, Liu Y, Gray LA, Aitken TJ, Chen Y, Beutler LR, Ahn JS, Madisen L, Zeng H, Krasnow MA, Knight ZA. Genetic Identification of Vagal Sensory Neurons That Control Feeding. Cell. 2019 Nov 14; 179(5):1129-1143.e23. PMID: 31730854. https://www.ncbi.nlm.nih.gov
60margd
A college room-mate studied "food science". I remember being amused by her summer job developing a new candy bar. No longer amused!
George Takei @GeorgeTakei | 11:19 PM · Dec 20, 2019
Which foods do you find to be the most addictive, friends?
These Are the Most Addictive Foods (3:25)
https://twitter.com/GeorgeTakei/status/1208240425883975681
--------------------------------------------------------------------------------
The Science of Addictive Food (11:12)
CBC News: The National • Mar 6, 2013
There's a science to making addictive food, a practice that convinces us to eat food that's bad for us because it tastes so good.
https://www.youtube.com/watch?v=4cpdb78pWl4
George Takei @GeorgeTakei | 11:19 PM · Dec 20, 2019
Which foods do you find to be the most addictive, friends?
These Are the Most Addictive Foods (3:25)
https://twitter.com/GeorgeTakei/status/1208240425883975681
--------------------------------------------------------------------------------
The Science of Addictive Food (11:12)
CBC News: The National • Mar 6, 2013
There's a science to making addictive food, a practice that convinces us to eat food that's bad for us because it tastes so good.
https://www.youtube.com/watch?v=4cpdb78pWl4
61margd
A man consuming a sugar-heavy diet for week before conception MAY produce overweight kids... It does in fruit flies, and some of the underlying changes (increase in small fragments of RNA, tsRNA, thought to have epigenetic effects) occur in men after just one week of a sugary diet....
Diet has rapid effects on sperm quality
Linköping University | December 27, 2019
Anita Öst, senior lecturer at Linköping University. Credit: Ulrik Svedin/LiU
Sperm are influenced by diet, and the effects arise rapidly. This is the conclusion of a study by researchers at Linköping University, in which healthy young men were fed a diet rich in sugar. The study,* which has been published in PLOS Biology, gives new insight into the function of sperm, and may in the long term contribute to new diagnostic methods to measure sperm quality.
"We see that diet influences the motility of the sperm, and we can link the changes to specific molecules in them. Our study has revealed rapid effects that are noticeable after one to two weeks," says Anita Öst, senior lecturer in the Department of Clinical and Experimental Medicine at Linköping University, and head of the study.
Sperm quality can be harmed by several environmental and lifestyle factors, of which obesity and related diseases, such as type 2 diabetes, are well-known risk factors for poor sperm quality. The research group that carried out the new study is interested in epigenetic phenomena, which involve physical properties or levels of gene expression changing, even when the genetic material, the DNA sequence, is not changed. In certain cases such epigenetic changes can lead to properties being transferred from a parent to offspring via the sperm or the egg.
In a previous study, the scientists showed that male fruit flies which had consumed excess sugar shortly before mating more often produced offspring who became overweight. Similar studies on mice have suggested that small fragments of RNA known as tsRNA play a role in these epigenetic phenomena that appear in the next generation. These RNA fragments are present in unusually large amounts in the sperm of many species, including humans, fruit flies and mice. So far, their function has not been examined in detail. Scientists have speculated that the RNA fragments in sperm may be involved in epigenetic phenomena, but it is too early to say whether this is the case in humans. The new study was initiated by the researchers to investigate whether a high consumption of sugar affects the RNA fragments in human sperm....
https://phys.org/news/2019-12-diet-rapid-effects-sperm-quality.html
__________________________________________________________________________
Nätt D, Kugelberg U, Casas E, Nedstrand E, Zalavary S, Henriksson P, et al. (2019) Human sperm displays rapid responses to diet. PLoS Biol 17(12): e3000559. https://doi.org/10.1371/journal.pbio.3000559 . https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000559
Abstract
The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.
...
Discussion
Here we show that human sperm are sensitive to nutritional flux, both in respect to sperm motility and the sncRNA pool. Such an acute responsiveness agrees with our earlier study in Drosophila, in which we showed that just 2 days of dietary intervention in male flies before mating was sufficient to transmit a signal through the sperm to induce metabolic reprogramming in the next generation 19. In the current study, we show that specific mitochondrial and nuclear tsRNAs in human sperm are independently up-regulated following a similar short-term diet intervention. The increase of these tsRNA was positively associated with sperm motility. Moreover, in nuclear tsRNAs, we identified sugar-sensitive cleavage in the T-loop of full-length nuclear tRNA, generating a short internal tsRNA, which we named nitRNA.
...
Is there a role for tsRNA in metabolic intergenerational effects in humans?
In mice, it has been shown that 5′-GlyGCC, which is abundant in sperm and affected by a low-protein diet, represses genes necessary for the proliferation of murine endogenous retroviruses in embryos and in embryonic stem cells 26. Moreover, short CCA-3′-tsRNAs have been shown to inhibit this type of retrotransposons in mouse preimplantation stem cells. It has, therefore, been proposed that tsRNA protects against reactivation of transposable elements during the reprogramming to a pluripotent stage. There are multiple lines of evidence connecting the regulation of transposable elements to metabolic phenotypes. First (and still one of the best examples of epigenetic inheritance of obesity) is the transgenerational control of a retrotransposon upstream of the agouti gene in mice. Moreover, SETDB1 and TRIM28 (also known as KAP1), which both repress retrotransposons, also modulate obesity in mice. Thus, it is possible that sperm tsRNAs—via direct control of retrotransposons, or genes harboring regulatory elements borrowed from retrotransposons—set long-term metabolic programs in the embryo that later define offspring obesity risks.
Considering the accumulating evidence of sncRNA being a mobile source of cell-to-cell communication, it is an intriguing idea that this communication is effective also from sperm to egg. This is robustly supported by studies in mice, but due to ethical constraint, such studies are difficult to perform on humans. Even though the recent study on embryo quality by Hua and colleagues supports this idea, conclusive evidence that the human egg cell is responding to changes in the pool of sperm sncRNA, or what has been termed the sncRNA code, is missing. We have, however, shown that human sperm has the plasticity to reconfigure the sperm sncRNA code in response to rapid environmental changes, which in other species has served as a message to the next generation. Most importantly, the paralleled response of sperm motility and shifts in the sncRNA code hints that there might be a shared etiology between male fertility and intergenerational metabolic responses.
We conclude that human sperm is acutely sensitive to dietary shifts and propose that this sensitivity involves an interplay between the sncRNA code and sperm function. This is likely driven by two independent pathways, divided by cellular compartmentation (nuclear/mitochondrial). Further exploration of these pathways may not only be critical in understanding the global decline in human sperm function but may provide a possible mechanism for rapid intergenerational metabolic responses so far only described in animals....
Diet has rapid effects on sperm quality
Linköping University | December 27, 2019
Anita Öst, senior lecturer at Linköping University. Credit: Ulrik Svedin/LiU
Sperm are influenced by diet, and the effects arise rapidly. This is the conclusion of a study by researchers at Linköping University, in which healthy young men were fed a diet rich in sugar. The study,* which has been published in PLOS Biology, gives new insight into the function of sperm, and may in the long term contribute to new diagnostic methods to measure sperm quality.
"We see that diet influences the motility of the sperm, and we can link the changes to specific molecules in them. Our study has revealed rapid effects that are noticeable after one to two weeks," says Anita Öst, senior lecturer in the Department of Clinical and Experimental Medicine at Linköping University, and head of the study.
Sperm quality can be harmed by several environmental and lifestyle factors, of which obesity and related diseases, such as type 2 diabetes, are well-known risk factors for poor sperm quality. The research group that carried out the new study is interested in epigenetic phenomena, which involve physical properties or levels of gene expression changing, even when the genetic material, the DNA sequence, is not changed. In certain cases such epigenetic changes can lead to properties being transferred from a parent to offspring via the sperm or the egg.
In a previous study, the scientists showed that male fruit flies which had consumed excess sugar shortly before mating more often produced offspring who became overweight. Similar studies on mice have suggested that small fragments of RNA known as tsRNA play a role in these epigenetic phenomena that appear in the next generation. These RNA fragments are present in unusually large amounts in the sperm of many species, including humans, fruit flies and mice. So far, their function has not been examined in detail. Scientists have speculated that the RNA fragments in sperm may be involved in epigenetic phenomena, but it is too early to say whether this is the case in humans. The new study was initiated by the researchers to investigate whether a high consumption of sugar affects the RNA fragments in human sperm....
https://phys.org/news/2019-12-diet-rapid-effects-sperm-quality.html
__________________________________________________________________________
Nätt D, Kugelberg U, Casas E, Nedstrand E, Zalavary S, Henriksson P, et al. (2019) Human sperm displays rapid responses to diet. PLoS Biol 17(12): e3000559. https://doi.org/10.1371/journal.pbio.3000559 . https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000559
Abstract
The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.
...
Discussion
Here we show that human sperm are sensitive to nutritional flux, both in respect to sperm motility and the sncRNA pool. Such an acute responsiveness agrees with our earlier study in Drosophila, in which we showed that just 2 days of dietary intervention in male flies before mating was sufficient to transmit a signal through the sperm to induce metabolic reprogramming in the next generation 19. In the current study, we show that specific mitochondrial and nuclear tsRNAs in human sperm are independently up-regulated following a similar short-term diet intervention. The increase of these tsRNA was positively associated with sperm motility. Moreover, in nuclear tsRNAs, we identified sugar-sensitive cleavage in the T-loop of full-length nuclear tRNA, generating a short internal tsRNA, which we named nitRNA.
...
Is there a role for tsRNA in metabolic intergenerational effects in humans?
In mice, it has been shown that 5′-GlyGCC, which is abundant in sperm and affected by a low-protein diet, represses genes necessary for the proliferation of murine endogenous retroviruses in embryos and in embryonic stem cells 26. Moreover, short CCA-3′-tsRNAs have been shown to inhibit this type of retrotransposons in mouse preimplantation stem cells. It has, therefore, been proposed that tsRNA protects against reactivation of transposable elements during the reprogramming to a pluripotent stage. There are multiple lines of evidence connecting the regulation of transposable elements to metabolic phenotypes. First (and still one of the best examples of epigenetic inheritance of obesity) is the transgenerational control of a retrotransposon upstream of the agouti gene in mice. Moreover, SETDB1 and TRIM28 (also known as KAP1), which both repress retrotransposons, also modulate obesity in mice. Thus, it is possible that sperm tsRNAs—via direct control of retrotransposons, or genes harboring regulatory elements borrowed from retrotransposons—set long-term metabolic programs in the embryo that later define offspring obesity risks.
Considering the accumulating evidence of sncRNA being a mobile source of cell-to-cell communication, it is an intriguing idea that this communication is effective also from sperm to egg. This is robustly supported by studies in mice, but due to ethical constraint, such studies are difficult to perform on humans. Even though the recent study on embryo quality by Hua and colleagues supports this idea, conclusive evidence that the human egg cell is responding to changes in the pool of sperm sncRNA, or what has been termed the sncRNA code, is missing. We have, however, shown that human sperm has the plasticity to reconfigure the sperm sncRNA code in response to rapid environmental changes, which in other species has served as a message to the next generation. Most importantly, the paralleled response of sperm motility and shifts in the sncRNA code hints that there might be a shared etiology between male fertility and intergenerational metabolic responses.
We conclude that human sperm is acutely sensitive to dietary shifts and propose that this sensitivity involves an interplay between the sncRNA code and sperm function. This is likely driven by two independent pathways, divided by cellular compartmentation (nuclear/mitochondrial). Further exploration of these pathways may not only be critical in understanding the global decline in human sperm function but may provide a possible mechanism for rapid intergenerational metabolic responses so far only described in animals....
62margd
Propionate is produced by bacteria in gut and is also added to foods like cheese as anti-mold agent. Always good to add fiber to our diet, but I'd read up more before trying propionate supplement. (It increases blood glucose?)
Supplement may help burn fat long after exercise
Gut bacteria produce an appetite suppressant than can strengthen the effect of an exercise-based weight loss program.
Robby Berman | January 17, 2020
...Moderate intensity exercise training programmes when combined with daily oral IPE supplementation may help overweight women to achieve increase in fat oxidation. explored a supplement called inulin-propionate ester (IPE).
Propionate is a short-chain fatty acid produced in the digestion of dietary fiber by gut microbes. It is a natural and effective appetite suppressor.
Propionate breaks down quickly in the body, so to strengthen its effect, scientists have chemically bound it to inulin. This is a fiber common to garlic, Jerusalem artichoke, chicory, and onion. The result is IPE.
...use of IPE as a dietary supplement increased the rate at which the body oxidizes, or burns, fat while at rest.
...suppresses the urge to consume high calorie foods. As an example, those who the researchers offered all the pasta they could eat wound up eating 10% less than they usually would.
Their new study has revealed that IPE can enhance the weight loss effects of a moderate exercise program without requiring dietary changes.
...The group taking the IPE...showed a significant increase in the burning of fat at rest, even 7 hours after their most recent dose of IPE.
...conclusions require additional verification...
https://www.medicalnewstoday.com/articles/327519.php#4
_______________________________________________________________
* Dalia Malkovaa et al. 2020. Moderate intensity exercise training combined with inulin-propionate ester supplementation increases whole body resting fat oxidation in overweight women. Metabolism Volume 104, March 2020, 154043. https://doi.org/10.1016/j.metabol.2019.154043
https://www.sciencedirect.com/science/article/abs/pii/S0026049519302586
Highlights
Exercise induced weight loss without caloric restriction remains controversial and responses are highly individual.
Maximising fat oxidation may enhance body fat mass loss alongside exercise in overweight and obese individuals.
We have previously shown that oral propionate increases fat oxidation, here we investigate the effects of colonic propionate.
Inulin propionate ester increases resting fat oxidation consistently in overweight exercising women compared with placebo.
Abstract
Background
Our previous work has shown that oral supplementation with inulin propionate ester (IPE) reduces intra-abdominal fat and prevents weight gain and that oral propionate intake enhances resting fat oxidation. The effects of IPE combined with exercise training on energy substrate utilisation are unknown. The aim of this study was to investigate the impact of 4-weeks IPE supplementation, in combination with a moderate intensity exercise training programme, on whole body fat oxidation and on plasma GLP-1 and PYY.
Methods
Twenty overweight healthy women participated in randomised parallel study and underwent 4 weeks of supervised exercise training either with IPE (EX/IPE group) or Placebo (EX/Placebo group) supplementation. Before and after the intervention participants conducted an experimental trial, which involved collection of expired gas and blood samples in the fasted state and during 7 h of the postprandial state.
Results
Within groups, the EX/IPE group significantly enhanced the amount of fat...oxidised and reduced CHO (carbohydrate?)...oxidised, reduced body weight...and body fat mass... In EX/Placebo group, changes in amount of fat...and CHO...oxidised, body weigh...and body fat mass...were not significant...Comparing between groups, changes in the amount of fat oxidised were significantly...different and a trend for difference was observed for amount of CHO oxidised... The interventions had no impact on fasting or postprandial plasma concentrations of GLP-1 and PYY.
Conclusion
Moderate intensity exercise training programmes when combined with daily oral IPE supplementation may help overweight women to achieve increase in fat oxidation.
Supplement may help burn fat long after exercise
Gut bacteria produce an appetite suppressant than can strengthen the effect of an exercise-based weight loss program.
Robby Berman | January 17, 2020
...Moderate intensity exercise training programmes when combined with daily oral IPE supplementation may help overweight women to achieve increase in fat oxidation. explored a supplement called inulin-propionate ester (IPE).
Propionate is a short-chain fatty acid produced in the digestion of dietary fiber by gut microbes. It is a natural and effective appetite suppressor.
Propionate breaks down quickly in the body, so to strengthen its effect, scientists have chemically bound it to inulin. This is a fiber common to garlic, Jerusalem artichoke, chicory, and onion. The result is IPE.
...use of IPE as a dietary supplement increased the rate at which the body oxidizes, or burns, fat while at rest.
...suppresses the urge to consume high calorie foods. As an example, those who the researchers offered all the pasta they could eat wound up eating 10% less than they usually would.
Their new study has revealed that IPE can enhance the weight loss effects of a moderate exercise program without requiring dietary changes.
...The group taking the IPE...showed a significant increase in the burning of fat at rest, even 7 hours after their most recent dose of IPE.
...conclusions require additional verification...
https://www.medicalnewstoday.com/articles/327519.php#4
_______________________________________________________________
* Dalia Malkovaa et al. 2020. Moderate intensity exercise training combined with inulin-propionate ester supplementation increases whole body resting fat oxidation in overweight women. Metabolism Volume 104, March 2020, 154043. https://doi.org/10.1016/j.metabol.2019.154043
https://www.sciencedirect.com/science/article/abs/pii/S0026049519302586
Highlights
Exercise induced weight loss without caloric restriction remains controversial and responses are highly individual.
Maximising fat oxidation may enhance body fat mass loss alongside exercise in overweight and obese individuals.
We have previously shown that oral propionate increases fat oxidation, here we investigate the effects of colonic propionate.
Inulin propionate ester increases resting fat oxidation consistently in overweight exercising women compared with placebo.
Abstract
Background
Our previous work has shown that oral supplementation with inulin propionate ester (IPE) reduces intra-abdominal fat and prevents weight gain and that oral propionate intake enhances resting fat oxidation. The effects of IPE combined with exercise training on energy substrate utilisation are unknown. The aim of this study was to investigate the impact of 4-weeks IPE supplementation, in combination with a moderate intensity exercise training programme, on whole body fat oxidation and on plasma GLP-1 and PYY.
Methods
Twenty overweight healthy women participated in randomised parallel study and underwent 4 weeks of supervised exercise training either with IPE (EX/IPE group) or Placebo (EX/Placebo group) supplementation. Before and after the intervention participants conducted an experimental trial, which involved collection of expired gas and blood samples in the fasted state and during 7 h of the postprandial state.
Results
Within groups, the EX/IPE group significantly enhanced the amount of fat...oxidised and reduced CHO (carbohydrate?)...oxidised, reduced body weight...and body fat mass... In EX/Placebo group, changes in amount of fat...and CHO...oxidised, body weigh...and body fat mass...were not significant...Comparing between groups, changes in the amount of fat oxidised were significantly...different and a trend for difference was observed for amount of CHO oxidised... The interventions had no impact on fasting or postprandial plasma concentrations of GLP-1 and PYY.
Conclusion
Moderate intensity exercise training programmes when combined with daily oral IPE supplementation may help overweight women to achieve increase in fat oxidation.
63margd
Reduce consumption of soybean oil?
One Of The Most Common Ingredients In The Western Diet Has Been Found To Alter Genes In The Brain
Ben Taub | 20 Jan 2020
...may be down to the way that soybean oil causes genetic changes in the brain.
...mice fed a diet that is high in soybean oil are much more likely to develop (metabolic conditions like diabetes, insulin resistance, and obesity) than rodents fed on other fats like coconut oil. Further studies hinted that the culprit may be linoleic acid, as mice that consumed soybean oil that had been modified to lack this key ingredient were spared many of these harmful effects.
...soybean oil was found to modify the expression of around 100 different genes in the hypothalamus, affecting processes such as metabolism, neurological disease, and inflammation.
Among the altered genes were some that are associated with schizophrenia, depression, and Alzheimer’s disease, although by far the most affected was a gene that codes for the production of a hormone called oxytocin.
Oxytocin is sometimes referred to as the “love hormone” ... However, it also plays a key role in regulating body weight and glucose metabolism, and mice fed on soybean oil were therefore found to suffer from glucose intolerance, while those fed on coconut oil had no such problems.
...linoleic acid ruled out...stigmasterol is not to blame for the dangers of soybean oil.
...author Poonamjot Deol of the University of California, Riverside says that while many questions remain unanswered, some very concrete statements can be made off the back of this study. "If there's one message I want people to take away, it's this: reduce consumption of soybean oil" ...
https://www.iflscience.com/health-and-medicine/one-most-common-ingredients-weste...
___________________________________________________________________________________
Poonamjot Deol et al. 2020. Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice. Endocrinology (accepted manuscript, Jan 8, 2020) https://doi.org/10.1210/endocr/bqz044 https://academic.oup.com/endo/advance-article/doi/10.1210/endocr/bqz044/5698148
Abstract
Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA-seq analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish) and coconut oil (high in saturated fat, containing no LA). The two soybean oil diets had similar, albeit non-identical, effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced while plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt mRNA levels could be associated with the diabetic state. Given its ubiquitous presence in the American diet, the observed effects of soybean oil on hypothalamic gene expression could have important public health ramifications.
One Of The Most Common Ingredients In The Western Diet Has Been Found To Alter Genes In The Brain
Ben Taub | 20 Jan 2020
...may be down to the way that soybean oil causes genetic changes in the brain.
...mice fed a diet that is high in soybean oil are much more likely to develop (metabolic conditions like diabetes, insulin resistance, and obesity) than rodents fed on other fats like coconut oil. Further studies hinted that the culprit may be linoleic acid, as mice that consumed soybean oil that had been modified to lack this key ingredient were spared many of these harmful effects.
...soybean oil was found to modify the expression of around 100 different genes in the hypothalamus, affecting processes such as metabolism, neurological disease, and inflammation.
Among the altered genes were some that are associated with schizophrenia, depression, and Alzheimer’s disease, although by far the most affected was a gene that codes for the production of a hormone called oxytocin.
Oxytocin is sometimes referred to as the “love hormone” ... However, it also plays a key role in regulating body weight and glucose metabolism, and mice fed on soybean oil were therefore found to suffer from glucose intolerance, while those fed on coconut oil had no such problems.
...linoleic acid ruled out...stigmasterol is not to blame for the dangers of soybean oil.
...author Poonamjot Deol of the University of California, Riverside says that while many questions remain unanswered, some very concrete statements can be made off the back of this study. "If there's one message I want people to take away, it's this: reduce consumption of soybean oil" ...
https://www.iflscience.com/health-and-medicine/one-most-common-ingredients-weste...
___________________________________________________________________________________
Poonamjot Deol et al. 2020. Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice. Endocrinology (accepted manuscript, Jan 8, 2020) https://doi.org/10.1210/endocr/bqz044 https://academic.oup.com/endo/advance-article/doi/10.1210/endocr/bqz044/5698148
Abstract
Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA-seq analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish) and coconut oil (high in saturated fat, containing no LA). The two soybean oil diets had similar, albeit non-identical, effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced while plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt mRNA levels could be associated with the diabetic state. Given its ubiquitous presence in the American diet, the observed effects of soybean oil on hypothalamic gene expression could have important public health ramifications.
64margd
So include lots of plant-based fiber in diet...Minimize sugars. etc.?
Studies have not yet been fully evaluated, so significant (?) that Nature published article on them already?
The microbes in your gut could predict whether you’re likely to die in the next 15 years
Rodrigo Pérez Ortega | Jan. 22, 2020 , 2:25 PM
...13 common diseases...Overall, the genetic signature of gut microbes was 20% better at discriminating between a healthy and an ill person than a person’s own genes, the team reports in a paper posted this month on the preprint server bioRxiv. The microbiome was 50% better than GWA (Genome-wide Association) studies at predicting whether someone had colorectal cancer. A person’s own genetic profile only outperformed the microbiome for predicting whether someone had type 1 diabetes...
...individuals with an abundance of Enterobacteriaceae bacteria—a family of potentially infectious bacteria that includes Escherichia coli and salmonella—are 15% more likely to die in the next 15 years ...
https://www.sciencemag.org/news/2020/01/microbes-your-gut-could-predict-whether-...
_______________________________________________________________________________
Braden T Tierney et al. Jan 2, 2020. The predictive power of the microbiome exceeds that of genome-wide association studies in the discrimination of complex human disease (preprint). BioRxiv doi: https://doi.org/10.1101/2019.12.31.891978 https://www.biorxiv.org/content/10.1101/2019.12.31.891978v1
This article is a preprint and has not been peer-reviewed.
It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Over the past decade, studies of the human genome and microbiome have deepened our understanding of the connections between human genes, environments, microbes, and disease. For example, the sheer number of indicators of the microbiome and human genetic common variants associated with disease has been immense, but clinical utility has been elusive. Here, we compared the predictive capabilities of the human microbiome versus human genomic common variants across 13 common diseases. We concluded that microbiomic indicators outperform human genetics in predicting host phenotype (overall Microbiome-Association-Study or MAS) area under the curve (AUC) = 0.79..., overall Genome-Wide-Association-Study (GWAS) AUC = 0.67. Our results, while preliminary and focused on a subset of the totality of disease, demonstrate the relative predictive ability of the microbiome, indicating that it may outperform human genetics in discriminating human disease cases and controls. They additionally motivate the need for population-level microbiome sequencing resources, akin to the UK Biobank, to further improve and reproduce metagenomic models of disease.
_______________________________________________________________________________
Aaro Salosensaari et al. 2020. Taxonomic Signatures of Long-Term Mortality Risk in Human Gut Microbiota (preprint). medRxiv. doi: https://doi.org/10.1101/2019.12.30.19015842 . https://www.medrxiv.org/content/10.1101/2019.12.30.19015842v2
This article is a preprint and has not been peer-reviewed.
It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
The collection of fecal material and developments in sequencing technologies have enabled cost-efficient, standardized, and non-invasive gut microbiome profiling. As a result, microbiome composition data from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterized due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a large, well-phenotyped, and representative population cohort (n = 7211, FINRISK 2002; Finland). We report specific taxonomic and functional signatures related to the Enterobacteriaceae family in the human gut microbiome that predict mortality during a 15-year follow-up. These associations can be observed both in the Eastern and Western Finns who have differing genetic backgrounds, lifestyles, and mortality rates. Our results supplement previously reported cross-sectional associations, and help to establish a methodological and conceptual basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status. These findings could serve as a solid framework for microbiome profiling in clinical risk prediction, paving the way towards clinical applications of human microbiome sequencing aimed at prediction, prevention, and treatment of disease.
Studies have not yet been fully evaluated, so significant (?) that Nature published article on them already?
The microbes in your gut could predict whether you’re likely to die in the next 15 years
Rodrigo Pérez Ortega | Jan. 22, 2020 , 2:25 PM
...13 common diseases...Overall, the genetic signature of gut microbes was 20% better at discriminating between a healthy and an ill person than a person’s own genes, the team reports in a paper posted this month on the preprint server bioRxiv. The microbiome was 50% better than GWA (Genome-wide Association) studies at predicting whether someone had colorectal cancer. A person’s own genetic profile only outperformed the microbiome for predicting whether someone had type 1 diabetes...
...individuals with an abundance of Enterobacteriaceae bacteria—a family of potentially infectious bacteria that includes Escherichia coli and salmonella—are 15% more likely to die in the next 15 years ...
https://www.sciencemag.org/news/2020/01/microbes-your-gut-could-predict-whether-...
_______________________________________________________________________________
Braden T Tierney et al. Jan 2, 2020. The predictive power of the microbiome exceeds that of genome-wide association studies in the discrimination of complex human disease (preprint). BioRxiv doi: https://doi.org/10.1101/2019.12.31.891978 https://www.biorxiv.org/content/10.1101/2019.12.31.891978v1
This article is a preprint and has not been peer-reviewed.
It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Over the past decade, studies of the human genome and microbiome have deepened our understanding of the connections between human genes, environments, microbes, and disease. For example, the sheer number of indicators of the microbiome and human genetic common variants associated with disease has been immense, but clinical utility has been elusive. Here, we compared the predictive capabilities of the human microbiome versus human genomic common variants across 13 common diseases. We concluded that microbiomic indicators outperform human genetics in predicting host phenotype (overall Microbiome-Association-Study or MAS) area under the curve (AUC) = 0.79..., overall Genome-Wide-Association-Study (GWAS) AUC = 0.67. Our results, while preliminary and focused on a subset of the totality of disease, demonstrate the relative predictive ability of the microbiome, indicating that it may outperform human genetics in discriminating human disease cases and controls. They additionally motivate the need for population-level microbiome sequencing resources, akin to the UK Biobank, to further improve and reproduce metagenomic models of disease.
_______________________________________________________________________________
Aaro Salosensaari et al. 2020. Taxonomic Signatures of Long-Term Mortality Risk in Human Gut Microbiota (preprint). medRxiv. doi: https://doi.org/10.1101/2019.12.30.19015842 . https://www.medrxiv.org/content/10.1101/2019.12.30.19015842v2
This article is a preprint and has not been peer-reviewed.
It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
The collection of fecal material and developments in sequencing technologies have enabled cost-efficient, standardized, and non-invasive gut microbiome profiling. As a result, microbiome composition data from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterized due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a large, well-phenotyped, and representative population cohort (n = 7211, FINRISK 2002; Finland). We report specific taxonomic and functional signatures related to the Enterobacteriaceae family in the human gut microbiome that predict mortality during a 15-year follow-up. These associations can be observed both in the Eastern and Western Finns who have differing genetic backgrounds, lifestyles, and mortality rates. Our results supplement previously reported cross-sectional associations, and help to establish a methodological and conceptual basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status. These findings could serve as a solid framework for microbiome profiling in clinical risk prediction, paving the way towards clinical applications of human microbiome sequencing aimed at prediction, prevention, and treatment of disease.
65margd
Lack of fiber in the diet affects the bacterial community in the colon. Liver and colon linked by omentum.*
Liver and omentum also populated with bacteria. Both liver and omentum are important for the regulation of metabolism.
"There was a clear difference in the bacterial signature between people with diabetes and those without."
Gut bacteria may be linked to type 2 diabetes
March 2020
A study has found that there may be an association between bacteria in parts of the body and type 2 diabetes.
The bacteria in our guts may play a role in the development of type 2 diabetes.
The latest research lays the ground for future work to determine what this relationship may be, how it functions, and in what ways it may help clinicians combat type 2 diabetes and other diseases that show an association with obesity.
...Bacterial signatures
For their study, the researchers took samples from 40 people who had severe obesity and, as a consequence, were undergoing bariatric surgery.
Half of the participants had type 2 diabetes, while the other half showed signs of insulin resistance but did not yet have diabetes.
The researchers took samples from three abdominal fat deposits, as well as the liver, and were looking to identify which particular type of bacteria resides in these tissues.
They hoped the investigations would allow them to determine a ‘bacterial signature’ for the sample sites of the various individuals.
The researchers found that there was a clear difference in the bacterial signature between people with diabetes and those without.
In particular, they found that the greatest amount of bacteria was in the liver and fatty material connecting the stomach and the colon (omentum*). Both these areas are important for the regulation of metabolism.
...The study authors suspect that the bacteria they found in the tissue of those individuals with diabetes came from their intestines.
The intestine is more permeable than other parts of a person’s body, and, according to a review in the journal Nutrition Research, may become more permeable if a person has obesity.
...Future research...
https://www.medicalnewstoday.com/articles/gut-bacteria-may-be-linked-to-type-2-d...
---------------------------------------------------------------------------------------
Fernando F. Anhê et al. 2020. Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity. Nature Metabolism volume 2, pages 233–242 (09 March 2020) https://www.nature.com/articles/s42255-020-0178-9
Abstract
Visceral obesity is a key risk factor for type 2 diabetes (T2D). Whereas gut dysbiosis appears to be instrumental for this relationship, whether gut-associated signatures translocate to extra-intestinal tissues and how this affects host metabolism remain elusive. Here we provide a comparative analysis of the microbial profile found in plasma, liver and in three distinct adipose tissues of individuals with morbid obesity. We explored how these tissue microbial signatures vary between individuals with normoglycaemia and those with T2D that were matched for body mass index. We identified tissue-specific signatures with higher bacterial load in the liver and omental* adipose tissue. Gut commensals, but also environmental bacteria, showed tissue- and T2D-specific compartmentalisation. T2D signatures were most evident in mesenteric adipose tissue, in which individuals with diabetes displayed reduced bacterial diversity concomitant with fewer Gram-positive bacteria, such as Faecalibacterium, as opposed to enhanced levels of typically opportunistic Gram-negative Enterobacteriaceae. Plasma samples of individuals with diabetes were similarly enriched in Enterobacteriaceae, including the pathobiont Escherichia–Shigella. Our work provides evidence for the presence of selective plasma and tissue microbial signatures in individuals with severe obesity and identifies new potential microbial targets and biomarkers of T2D.
* "The greater omentum (also the great omentum, omentum majus, gastrocolic omentum, epiploon, or, especially in animals, caul) is a large apron-like fold of visceral peritoneum that hangs down from the stomach. It extends from the greater curvature of the stomach, passing in front of the small intestines and doubles back to ascend to the transverse colon before reaching to the posterior abdominal wall. The greater omentum is larger than the lesser omentum, which hangs down from the liver to the lesser curvature. The common anatomical term "epiploic" derives from "epiploon", from the Greek epipleein, meaning to float or sail on, since the greater omentum appears to float on the surface of the intestines. It is the first structure observed when the abdominal cavity is opened anteriorly." (See drawing at wikipedia--really quite a structure!)
Liver and omentum also populated with bacteria. Both liver and omentum are important for the regulation of metabolism.
"There was a clear difference in the bacterial signature between people with diabetes and those without."
Gut bacteria may be linked to type 2 diabetes
March 2020
A study has found that there may be an association between bacteria in parts of the body and type 2 diabetes.
The bacteria in our guts may play a role in the development of type 2 diabetes.
The latest research lays the ground for future work to determine what this relationship may be, how it functions, and in what ways it may help clinicians combat type 2 diabetes and other diseases that show an association with obesity.
...Bacterial signatures
For their study, the researchers took samples from 40 people who had severe obesity and, as a consequence, were undergoing bariatric surgery.
Half of the participants had type 2 diabetes, while the other half showed signs of insulin resistance but did not yet have diabetes.
The researchers took samples from three abdominal fat deposits, as well as the liver, and were looking to identify which particular type of bacteria resides in these tissues.
They hoped the investigations would allow them to determine a ‘bacterial signature’ for the sample sites of the various individuals.
The researchers found that there was a clear difference in the bacterial signature between people with diabetes and those without.
In particular, they found that the greatest amount of bacteria was in the liver and fatty material connecting the stomach and the colon (omentum*). Both these areas are important for the regulation of metabolism.
...The study authors suspect that the bacteria they found in the tissue of those individuals with diabetes came from their intestines.
The intestine is more permeable than other parts of a person’s body, and, according to a review in the journal Nutrition Research, may become more permeable if a person has obesity.
...Future research...
https://www.medicalnewstoday.com/articles/gut-bacteria-may-be-linked-to-type-2-d...
---------------------------------------------------------------------------------------
Fernando F. Anhê et al. 2020. Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity. Nature Metabolism volume 2, pages 233–242 (09 March 2020) https://www.nature.com/articles/s42255-020-0178-9
Abstract
Visceral obesity is a key risk factor for type 2 diabetes (T2D). Whereas gut dysbiosis appears to be instrumental for this relationship, whether gut-associated signatures translocate to extra-intestinal tissues and how this affects host metabolism remain elusive. Here we provide a comparative analysis of the microbial profile found in plasma, liver and in three distinct adipose tissues of individuals with morbid obesity. We explored how these tissue microbial signatures vary between individuals with normoglycaemia and those with T2D that were matched for body mass index. We identified tissue-specific signatures with higher bacterial load in the liver and omental* adipose tissue. Gut commensals, but also environmental bacteria, showed tissue- and T2D-specific compartmentalisation. T2D signatures were most evident in mesenteric adipose tissue, in which individuals with diabetes displayed reduced bacterial diversity concomitant with fewer Gram-positive bacteria, such as Faecalibacterium, as opposed to enhanced levels of typically opportunistic Gram-negative Enterobacteriaceae. Plasma samples of individuals with diabetes were similarly enriched in Enterobacteriaceae, including the pathobiont Escherichia–Shigella. Our work provides evidence for the presence of selective plasma and tissue microbial signatures in individuals with severe obesity and identifies new potential microbial targets and biomarkers of T2D.
* "The greater omentum (also the great omentum, omentum majus, gastrocolic omentum, epiploon, or, especially in animals, caul) is a large apron-like fold of visceral peritoneum that hangs down from the stomach. It extends from the greater curvature of the stomach, passing in front of the small intestines and doubles back to ascend to the transverse colon before reaching to the posterior abdominal wall. The greater omentum is larger than the lesser omentum, which hangs down from the liver to the lesser curvature. The common anatomical term "epiploic" derives from "epiploon", from the Greek epipleein, meaning to float or sail on, since the greater omentum appears to float on the surface of the intestines. It is the first structure observed when the abdominal cavity is opened anteriorly." (See drawing at wikipedia--really quite a structure!)
66margd
Follow your gut: Newly identified digestive-brain axis controls food choice
Champalimaud Centre for the Unknown | April 6, 2020
..."The mouth is the first checkpoint—deciding whether the food should be accepted or rejected," explains (Albino Oliveira-Maia, head of the Neuropsychiatry Unit at the Champalimaud Centre for the Unknown in Lisbon, Portugal). "Once inside, the food is broken up into nutrients, and the post-ingestive phase begins. "In this phase, it's the digestive system's turn to 'taste' the food and talk to the brain about your meal choice."
...post-ingestive processes can be divided into two types. The first deals with the present—how nutritious the food is and how much of it should be consumed. The second is a learning process that determines how the organism should respond to the same food in the future.
...a task in which animals would press levers to receive a direct injection of food into their stomach...even though the mice were not able to taste the food, they ended up spending their efforts on the "high-calorie" lever...established a new form of post-ingestive learning.
...the physiological mechanism...how information about the nutritional value of the food reaches the brain...the vagus nerve...a long nerve that forms bi-directional connections between the brain and multiple internal organs
"Different parts of the gut may have incomplete information about the nutritional value of the food that is being eaten. The liver, on the other hand, metabolically filters the blood arriving from most of the gut. This means that it's well-positioned to function as an overall metabolic sensor"...
...when the team tested their hypothesis by lesioning the hepatic branch of the vagus nerve, the mice were unable to acquire this new type of learning. This supported their assumption that this specific branch (of the vagus nerve) is the one sensing and relaying post-ingestive signals to the brain during the learning process.
...(dopamine) neurons were sensitive to post-ingestive signals, but also that their activity was necessary for the learning to occur....(When) the hepatic branch of the vagus nerve...was cut, the neurons' response to post-ingestive signals was significantly reduced.
...activation of dopamine neurons when nutrients reach the gut is critical for driving food-seeking behaviors."
Together, the results of the study reveal a novel learning process—orchestrated between the digestive system and the brain—that compels animals to seek out food that they never actually tasted. This testifies to the potency of the subconscious processes that control behavior...
https://medicalxpress.com/news/2020-04-gut-newly-digestive-brain-axis-food.html
---------------------------------------------------------------------------------------------------------
Ana B. Fernandes et al. Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron Activity, Neuron (2020). DOI: 10.1016/j.neuron.2020.03.009 https://www.cell.com/neuron/pdf/S0896-6273(20)30216-6.pdf
Highlights
• Postingestive sucrose can sustain operant food-seeking behavior
• Intragastric injection of sucrose activates a subpopulation of VTA dopamine neurons
• VTA dopamine neuron bursting is necessary for postingestive-dependent food seeking
• Postingestive modulation of dopamine neuron activity and food seeking is vagus-mediated
Summary
Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly after administration of intragastric sucrose, and deletion of the NMDA receptor in these neurons, which affects bursting and plasticity, abolishes lever pressing for postingestive sucrose delivery. Furthermore, lesions of the hepatic branch of the vagus nerve significantly impair postingestive-dependent VTA dopamine neuron activity and food seeking, whereas optogenetic stimulation of left vagus nerve neurons significantly increases VTA dopamine neuron activity. These data establish a necessary role of vagus-mediated dopamine neuron activity in postingestive-dependent food seeking, which is independent of taste signaling.
Champalimaud Centre for the Unknown | April 6, 2020
..."The mouth is the first checkpoint—deciding whether the food should be accepted or rejected," explains (Albino Oliveira-Maia, head of the Neuropsychiatry Unit at the Champalimaud Centre for the Unknown in Lisbon, Portugal). "Once inside, the food is broken up into nutrients, and the post-ingestive phase begins. "In this phase, it's the digestive system's turn to 'taste' the food and talk to the brain about your meal choice."
...post-ingestive processes can be divided into two types. The first deals with the present—how nutritious the food is and how much of it should be consumed. The second is a learning process that determines how the organism should respond to the same food in the future.
...a task in which animals would press levers to receive a direct injection of food into their stomach...even though the mice were not able to taste the food, they ended up spending their efforts on the "high-calorie" lever...established a new form of post-ingestive learning.
...the physiological mechanism...how information about the nutritional value of the food reaches the brain...the vagus nerve...a long nerve that forms bi-directional connections between the brain and multiple internal organs
"Different parts of the gut may have incomplete information about the nutritional value of the food that is being eaten. The liver, on the other hand, metabolically filters the blood arriving from most of the gut. This means that it's well-positioned to function as an overall metabolic sensor"...
...when the team tested their hypothesis by lesioning the hepatic branch of the vagus nerve, the mice were unable to acquire this new type of learning. This supported their assumption that this specific branch (of the vagus nerve) is the one sensing and relaying post-ingestive signals to the brain during the learning process.
...(dopamine) neurons were sensitive to post-ingestive signals, but also that their activity was necessary for the learning to occur....(When) the hepatic branch of the vagus nerve...was cut, the neurons' response to post-ingestive signals was significantly reduced.
...activation of dopamine neurons when nutrients reach the gut is critical for driving food-seeking behaviors."
Together, the results of the study reveal a novel learning process—orchestrated between the digestive system and the brain—that compels animals to seek out food that they never actually tasted. This testifies to the potency of the subconscious processes that control behavior...
https://medicalxpress.com/news/2020-04-gut-newly-digestive-brain-axis-food.html
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Ana B. Fernandes et al. Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron Activity, Neuron (2020). DOI: 10.1016/j.neuron.2020.03.009 https://www.cell.com/neuron/pdf/S0896-6273(20)30216-6.pdf
Highlights
• Postingestive sucrose can sustain operant food-seeking behavior
• Intragastric injection of sucrose activates a subpopulation of VTA dopamine neurons
• VTA dopamine neuron bursting is necessary for postingestive-dependent food seeking
• Postingestive modulation of dopamine neuron activity and food seeking is vagus-mediated
Summary
Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly after administration of intragastric sucrose, and deletion of the NMDA receptor in these neurons, which affects bursting and plasticity, abolishes lever pressing for postingestive sucrose delivery. Furthermore, lesions of the hepatic branch of the vagus nerve significantly impair postingestive-dependent VTA dopamine neuron activity and food seeking, whereas optogenetic stimulation of left vagus nerve neurons significantly increases VTA dopamine neuron activity. These data establish a necessary role of vagus-mediated dopamine neuron activity in postingestive-dependent food seeking, which is independent of taste signaling.
67margd
At some point, unintentional weight loss can be a problem for older people. Mouse study below explores small-intestine changes and restorative benefits of short-term (one month) dietary restriction FOLLOWED BY REFEEDING. Also discusses effects of ketogenetic diets (last paragraph), which I hesitate to characterize. (Maybe I'll come back to it. ;-)
Aging and diet lead to proteome changes in the intestinal epithelium
Fritz Lipmann Institute | May 1, 2020
...aging leads to reduced absorption of nutrients by the epithelium thus contributing to malnutrition in elderly people.
...Using state-of-the-art mass spectrometry-based proteomics, the research team investigated age- and region-specific differences in the cellular composition of intestinal crypts, anatomical structures beneath the absorptive epithelium, where intestinal stem cells (ISCs) and differentiated cell types are located. Their results provide a complete picture of the spatial organization of the SI (small intestine) proteome* in mouse...
Region-specific effects of aging on the intestinal epithelium
..."Our results show a clear effect of aging on the set of proteins and cellular composition of intestinal crypts. We found some major changes in inflammation-related proteins and decreased levels of stem cell markers. This shows that the delicate structure of the epithelium gets disturbed during aging, which leads to inflammation and reduced self-regeneration. Especially the region of the ileum* shows a more pronounced aging phenotype by a decreased number of goblet cells per crypt," says Nadja Gebert, first author of the study...
Effects of diet on the intestine of old and young mice
..."Especially the alternation between the dietary restricted and fed state, rather than dietary restriction alone, promotes a positive restoration of epithelium composition and a partial rejuvenation of the crypt proteome in old mice. This might be interpreted as support for the positive effects of interventions based on intermitted fasting. On the other hand, the reduced adaptive response of the old intestinal epithelium shows the drastic impact on the way old individuals are influenced by dietary changes or drug treatments," says Dr. Alessandro Ori, group leader at FLI (Leibniz Institute on Aging—Fritz Lipmann Institute)...
Ketone bodies regulate stem cell lineage decisions
Taking a closer insight into the processes affecting ISCs under short-term dietary restriction followed by refeeding, the researchers show that the epithelium is partially restored because of increased stem cell differentiation towards the secretory lineage. They identified the rate-limiting enzyme for ketogenesis, Hmgcs2, as a modulator of stem cell differentiation, which responds to dietary changes. Diet leads to increased levels of this enzyme in ISCs and a co-occurring reduction of all differentiation markers with exception of enterocyte* markers.
"We demonstrate that the activity of Hmgcs2 regulates ISC regeneration and differentiation in vitro, and the reduced activity of this enzyme promotes the expression of secretory markers both in vitro and in vivo. Our data show, that the reduced activity of Hmgcs2 modulates the differentiation of ISCs towards the secretory lineage," explains Gebert.
Taking a broader look at metabolic changes, the researchers found regional differences in the abundance of rate-limiting enzymes for other key metabolic pathways, e.g., gluconeogenesis. This suggests that the metabolism of intestinal epithelial cells and the levels of metabolites vary along the SI. These differences can contribute to the maintenance of the epithelial composition and the adaptation of the SI to changes of diet.
"With this broad proteomics study we are able to provide an atlas of the spatial organization of the small intestine proteome in mouse, which can be used for further studies and is available as free online resource," says Ori. The researchers will base future studies on the search for medical interventions capable of restoring the regenerative capacity of the old intestine, contributing to a healthy lifespan in the elderly.
https://medicalxpress.com/news/2020-05-aging-diet-proteome-intestinal-epithelium...
*
proteome--proteins in a given type of cell or organism, at a given time, under defined conditions
ileum--last anatomical part of small intestine, i.e., duodenum, jejunum and ileum.
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its surface area. (Wikipedia)
_______________________________________________________________
Nadja Gebert et al. Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction, Cell Reports (2020). DOI: 10.1016/j.celrep.2020.107565 https://www.cell.com/cell-reports/pdf/S2211-1247(20)30514-3.pdf
(See graphical abstract at link.)
In Brief
Using proteomics, Gebert et al. find that aging has region-specific effects on the small intestine epithelium of mice. These effects can be partially reversed by modulating ketone body signaling in intestinal stem cells via dietary intervention
Abstract
Highlights
The effects of aging on the small intestine are region specific.
Reduced plasticity of the old intestine to changes of diet.
Dietary restriction followed by refeeding restores goblet cells in old mice.
Ketone bodies prevent intestinal stem cells from differentiation into secretory cells
SUMMARY
The small intestine is responsible for nutrient absorption and one of the most important interfaces between the environment and the body. During aging, changes of the epithelium lead to food malabsorption and reduced barrier function, thus increasing disease risk. The drivers of these alterations remain poorly understood. Here, we compare the proteomes of intestinal crypts from mice across different anatomical regions and ages. We find that aging alters epithelial immunity, metabolism, and cell proliferation and is accompanied by region-dependent skewing in the cellular composition of the epithelium. Of note, short-term dietary re-striction followed by refeeding partially restores the epithelium by promoting stem cell differentiation toward the secretory lineage. We identify Hmgcs2 (3-hydroxy-3-methylglutaryl-coenzyme A CoA synthetase 2), the rate-limiting enzyme for ketogenesis, as a modulator of stem cell differentiation that responds to dietary changes, and we provide an atlas of region- and age-dependent proteome changes of the small intestine.
DISCUSSION
...Although both young andold animals respond to DR (dietary restriction), the response of old animals appears to be diminished both at the organismal level, as indicated by areduced capability to stabilize body weight, as well as at the intestinal level, as indicated by a reduced response of the cryptproteome.
...DR induced a proteome signature in both young and old animals that was similar to the one that we observed during aging. This suggests that DR of old animals is potentially aggravating aging-related changes
...Our data indicate that the alternation between the fasted and fed state, rather than DR per se, promotes a restoration of epithelium composition and a partial rejuvenation of the crypt proteome when applied to old animals. It is tempting to speculate that these effects might contribute, at least in part, to the health-promoting effects of dietary interventions based on intermitted fasting.
...In addition to the already known effects of DR on ISCs (intestinal stem cells') regenerative capacity...we show that changes of diet can also influence the differentiation of ISCs. Mechanistically, we directly link diet-induced changes in the levels of the mitochondrial enzyme Hmgcs2 and its downstream metabolite, OHB, to ISC differentiation. Hmgcs2 has been previously shown to influence the differentiation* of colorectal cancer cell lines in vitro and differentiation behavior of ISCs in vivo in young animals that underwent a ketogenic diet. Here, we show that treatment of mice with DR leads to increased levels of Hmgcs2 in ISCs and a co-occurring reduction of all differentiation markers, with the exception of enterocyte markers. Subsequent refeeding of mice that underwent DR rapidly reduces Hmgcs2 protein levels in ISCs and progenitor cells and increases the expression of Paneth and goblet cellmarkers in ISCs, leading to restoration of goblet cell numbers in ileal crypts. Using organoid cultures, we confirmed that pharmacological inhibition of Hmgcs2 is sufficient to reduce organoid-forming capacity and branching and to promote the differentiation toward the secretory lineage. These effects were comparable to the one induced by gamma secretase inhibition in vitro, reverted by OHB supplementation, and recapitulated in vivo using a genetic model of Hmgcs2 depletion. Recently, Cheng et al. demonstrated that the effect of Hmgcs2 on ISCs is mediated by epigenetic modulation of Notch signaling via the histone deacetylase inhibitor activity of OHB. Our work demonstrates that this metabolite-mediated mechanism contributes to the adaptation of the SI to changes of diet under physiological conditions. Similar mechanisms linking metabolic changes to modulation of developmental pathways via epigenetic alterations might extend beyond the SI and contribute to aging phenotypes in other stem cell compartments.
*
Differentiated cancer: A cancer in which the cells are mature and look like cells in the tissue from it arose. Differentiated cancers tend to be decidedly less aggressive than undifferentiated cancers composed of immature cells. (MedicineNet)
Aging and diet lead to proteome changes in the intestinal epithelium
Fritz Lipmann Institute | May 1, 2020
...aging leads to reduced absorption of nutrients by the epithelium thus contributing to malnutrition in elderly people.
...Using state-of-the-art mass spectrometry-based proteomics, the research team investigated age- and region-specific differences in the cellular composition of intestinal crypts, anatomical structures beneath the absorptive epithelium, where intestinal stem cells (ISCs) and differentiated cell types are located. Their results provide a complete picture of the spatial organization of the SI (small intestine) proteome* in mouse...
Region-specific effects of aging on the intestinal epithelium
..."Our results show a clear effect of aging on the set of proteins and cellular composition of intestinal crypts. We found some major changes in inflammation-related proteins and decreased levels of stem cell markers. This shows that the delicate structure of the epithelium gets disturbed during aging, which leads to inflammation and reduced self-regeneration. Especially the region of the ileum* shows a more pronounced aging phenotype by a decreased number of goblet cells per crypt," says Nadja Gebert, first author of the study...
Effects of diet on the intestine of old and young mice
..."Especially the alternation between the dietary restricted and fed state, rather than dietary restriction alone, promotes a positive restoration of epithelium composition and a partial rejuvenation of the crypt proteome in old mice. This might be interpreted as support for the positive effects of interventions based on intermitted fasting. On the other hand, the reduced adaptive response of the old intestinal epithelium shows the drastic impact on the way old individuals are influenced by dietary changes or drug treatments," says Dr. Alessandro Ori, group leader at FLI (Leibniz Institute on Aging—Fritz Lipmann Institute)...
Ketone bodies regulate stem cell lineage decisions
Taking a closer insight into the processes affecting ISCs under short-term dietary restriction followed by refeeding, the researchers show that the epithelium is partially restored because of increased stem cell differentiation towards the secretory lineage. They identified the rate-limiting enzyme for ketogenesis, Hmgcs2, as a modulator of stem cell differentiation, which responds to dietary changes. Diet leads to increased levels of this enzyme in ISCs and a co-occurring reduction of all differentiation markers with exception of enterocyte* markers.
"We demonstrate that the activity of Hmgcs2 regulates ISC regeneration and differentiation in vitro, and the reduced activity of this enzyme promotes the expression of secretory markers both in vitro and in vivo. Our data show, that the reduced activity of Hmgcs2 modulates the differentiation of ISCs towards the secretory lineage," explains Gebert.
Taking a broader look at metabolic changes, the researchers found regional differences in the abundance of rate-limiting enzymes for other key metabolic pathways, e.g., gluconeogenesis. This suggests that the metabolism of intestinal epithelial cells and the levels of metabolites vary along the SI. These differences can contribute to the maintenance of the epithelial composition and the adaptation of the SI to changes of diet.
"With this broad proteomics study we are able to provide an atlas of the spatial organization of the small intestine proteome in mouse, which can be used for further studies and is available as free online resource," says Ori. The researchers will base future studies on the search for medical interventions capable of restoring the regenerative capacity of the old intestine, contributing to a healthy lifespan in the elderly.
https://medicalxpress.com/news/2020-05-aging-diet-proteome-intestinal-epithelium...
*
proteome--proteins in a given type of cell or organism, at a given time, under defined conditions
ileum--last anatomical part of small intestine, i.e., duodenum, jejunum and ileum.
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its surface area. (Wikipedia)
_______________________________________________________________
Nadja Gebert et al. Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction, Cell Reports (2020). DOI: 10.1016/j.celrep.2020.107565 https://www.cell.com/cell-reports/pdf/S2211-1247(20)30514-3.pdf
(See graphical abstract at link.)
In Brief
Using proteomics, Gebert et al. find that aging has region-specific effects on the small intestine epithelium of mice. These effects can be partially reversed by modulating ketone body signaling in intestinal stem cells via dietary intervention
Abstract
Highlights
The effects of aging on the small intestine are region specific.
Reduced plasticity of the old intestine to changes of diet.
Dietary restriction followed by refeeding restores goblet cells in old mice.
Ketone bodies prevent intestinal stem cells from differentiation into secretory cells
SUMMARY
The small intestine is responsible for nutrient absorption and one of the most important interfaces between the environment and the body. During aging, changes of the epithelium lead to food malabsorption and reduced barrier function, thus increasing disease risk. The drivers of these alterations remain poorly understood. Here, we compare the proteomes of intestinal crypts from mice across different anatomical regions and ages. We find that aging alters epithelial immunity, metabolism, and cell proliferation and is accompanied by region-dependent skewing in the cellular composition of the epithelium. Of note, short-term dietary re-striction followed by refeeding partially restores the epithelium by promoting stem cell differentiation toward the secretory lineage. We identify Hmgcs2 (3-hydroxy-3-methylglutaryl-coenzyme A CoA synthetase 2), the rate-limiting enzyme for ketogenesis, as a modulator of stem cell differentiation that responds to dietary changes, and we provide an atlas of region- and age-dependent proteome changes of the small intestine.
DISCUSSION
...Although both young andold animals respond to DR (dietary restriction), the response of old animals appears to be diminished both at the organismal level, as indicated by areduced capability to stabilize body weight, as well as at the intestinal level, as indicated by a reduced response of the cryptproteome.
...DR induced a proteome signature in both young and old animals that was similar to the one that we observed during aging. This suggests that DR of old animals is potentially aggravating aging-related changes
...Our data indicate that the alternation between the fasted and fed state, rather than DR per se, promotes a restoration of epithelium composition and a partial rejuvenation of the crypt proteome when applied to old animals. It is tempting to speculate that these effects might contribute, at least in part, to the health-promoting effects of dietary interventions based on intermitted fasting.
...In addition to the already known effects of DR on ISCs (intestinal stem cells') regenerative capacity...we show that changes of diet can also influence the differentiation of ISCs. Mechanistically, we directly link diet-induced changes in the levels of the mitochondrial enzyme Hmgcs2 and its downstream metabolite, OHB, to ISC differentiation. Hmgcs2 has been previously shown to influence the differentiation* of colorectal cancer cell lines in vitro and differentiation behavior of ISCs in vivo in young animals that underwent a ketogenic diet. Here, we show that treatment of mice with DR leads to increased levels of Hmgcs2 in ISCs and a co-occurring reduction of all differentiation markers, with the exception of enterocyte markers. Subsequent refeeding of mice that underwent DR rapidly reduces Hmgcs2 protein levels in ISCs and progenitor cells and increases the expression of Paneth and goblet cellmarkers in ISCs, leading to restoration of goblet cell numbers in ileal crypts. Using organoid cultures, we confirmed that pharmacological inhibition of Hmgcs2 is sufficient to reduce organoid-forming capacity and branching and to promote the differentiation toward the secretory lineage. These effects were comparable to the one induced by gamma secretase inhibition in vitro, reverted by OHB supplementation, and recapitulated in vivo using a genetic model of Hmgcs2 depletion. Recently, Cheng et al. demonstrated that the effect of Hmgcs2 on ISCs is mediated by epigenetic modulation of Notch signaling via the histone deacetylase inhibitor activity of OHB. Our work demonstrates that this metabolite-mediated mechanism contributes to the adaptation of the SI to changes of diet under physiological conditions. Similar mechanisms linking metabolic changes to modulation of developmental pathways via epigenetic alterations might extend beyond the SI and contribute to aging phenotypes in other stem cell compartments.
*
Differentiated cancer: A cancer in which the cells are mature and look like cells in the tissue from it arose. Differentiated cancers tend to be decidedly less aggressive than undifferentiated cancers composed of immature cells. (MedicineNet)
68margd
When You Eat Breakfast and Dinner Could Affect Your Levels of Body Fat
Time to consider postponing brunch.
Emma Betuel | 8.31.2018
...you don’t have to become a disciple of the intermittent fasting dogma to reap the benefits of what they call “time restricted feeding” (TRF).
The team asked ten individuals to delay breakfast by 90 minutes and eat dinner 90 minutes earlier than usual. Results revealed that all those who were able to stick to the schedule reduced their overall body fat by the end of the ten weeks by an average of 1.9 percent.
“This was corroborated by questionnaire responses with 57% of participants noting a reduction in food intake either due to reduced appetite, reduced duration of eating opportunities and/or reduced snacking (particularly in the evening),” the authors wrote.
...why body fat decreased...could just be a matter of eating less (even though there were no restrictions)...the body burns through food at a faster metabolic rate earlier in the day (diet-induced thermogenesis was approximately twice as large in the morning at 0800h compared with in the evening at 2000h).
...Fifty seven percent of individuals admitted that they didn’t think they could continue these meal time changes past the end of ten weeks. They also rated the diet a seven out of ten on a scale of difficulty. Seeing as the authors described this group of volunteers as “well-motivated” to follow the diet, these results might not bode well for the rest of us...
https://www.inverse.com/article/48529-does-it-matter-when-you-eat-intermittent-f...
---------------------------------------------------------------------
Rona Antoni et al. 2018. A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects. Journal of Nutritional Science(2018), vol. 7, e22, 6 p. doi:10.1017/jns.2018.13 https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9C604826...
Abstract
This pilot study explored the feasibility of a moderate time-restricted feeding (TRF) intervention and its effects on adiposity and metabolism. For10 weeks,a free-living TRF group delayed breakfast and advanced dinner by 1·5 h each. Changes in dietary intake, adiposity and fasting biochemistry (glucose, insulin,lipids) were compared with controls who maintained habitual feeding patterns. Thirteen participants (29 (SEM2) kg/m2) completed the study. The average daily feeding interval was successfully reduced in the TRF group (743 (SEM32) to 517 (SEM22) min/d;P less than 0·001;n7), although questionnaire responses indicated that social eating/drinking opportunities were negatively impacted. TRF participants reduced total daily energy intake (P=0·019) despite ad libitum food access, with accompanying reductions in adiposity (P=0·047). There were significant between-group differences in fasting glucose (P=0·008), albeit driven primarily by an increase among controls. Larger studies can now be designed/powered, based on these novel preliminary qualitative and quantitative data, to ascertain and maximise the long-term sustainability of TRF.
Time to consider postponing brunch.
Emma Betuel | 8.31.2018
...you don’t have to become a disciple of the intermittent fasting dogma to reap the benefits of what they call “time restricted feeding” (TRF).
The team asked ten individuals to delay breakfast by 90 minutes and eat dinner 90 minutes earlier than usual. Results revealed that all those who were able to stick to the schedule reduced their overall body fat by the end of the ten weeks by an average of 1.9 percent.
“This was corroborated by questionnaire responses with 57% of participants noting a reduction in food intake either due to reduced appetite, reduced duration of eating opportunities and/or reduced snacking (particularly in the evening),” the authors wrote.
...why body fat decreased...could just be a matter of eating less (even though there were no restrictions)...the body burns through food at a faster metabolic rate earlier in the day (diet-induced thermogenesis was approximately twice as large in the morning at 0800h compared with in the evening at 2000h).
...Fifty seven percent of individuals admitted that they didn’t think they could continue these meal time changes past the end of ten weeks. They also rated the diet a seven out of ten on a scale of difficulty. Seeing as the authors described this group of volunteers as “well-motivated” to follow the diet, these results might not bode well for the rest of us...
https://www.inverse.com/article/48529-does-it-matter-when-you-eat-intermittent-f...
---------------------------------------------------------------------
Rona Antoni et al. 2018. A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects. Journal of Nutritional Science(2018), vol. 7, e22, 6 p. doi:10.1017/jns.2018.13 https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9C604826...
Abstract
This pilot study explored the feasibility of a moderate time-restricted feeding (TRF) intervention and its effects on adiposity and metabolism. For10 weeks,a free-living TRF group delayed breakfast and advanced dinner by 1·5 h each. Changes in dietary intake, adiposity and fasting biochemistry (glucose, insulin,lipids) were compared with controls who maintained habitual feeding patterns. Thirteen participants (29 (SEM2) kg/m2) completed the study. The average daily feeding interval was successfully reduced in the TRF group (743 (SEM32) to 517 (SEM22) min/d;P less than 0·001;n7), although questionnaire responses indicated that social eating/drinking opportunities were negatively impacted. TRF participants reduced total daily energy intake (P=0·019) despite ad libitum food access, with accompanying reductions in adiposity (P=0·047). There were significant between-group differences in fasting glucose (P=0·008), albeit driven primarily by an increase among controls. Larger studies can now be designed/powered, based on these novel preliminary qualitative and quantitative data, to ascertain and maximise the long-term sustainability of TRF.
69margd
Obesity is linked to gut microbiota disturbance, but not among statin-treated individuals
VIB (the Flanders Institute for Biotechnology) | May 6, 2020
...Exploring gut microbiota configurations of lean and obese volunteers, the MetaCardis researchers observed that Bact2 (Bacteroides2) prevalence increased with BMI. While only 4% of lean and overweight subjects were characterized as Bact2 carriers, percentages sharply rose to 19% among obese volunteers....
Sara Vieira-Silva (principal author, VIB-KU Leuven): "We found systemic inflammation in participants carrying the Bact2 enterotype to be higher than expected based on their BMI. Even though this study design does not allow inferring causality, our analyses do suggest that gut bacteria play a role in the process of developing obesity-associated comorbidities by sustaining inflammation. While these key findings confirmed our study hypothesis, the results we obtained when comparing statin-treated and -untreated participants came as a total surprise."
Statins are commonly prescribed to reduce risk of developing cardio-metabolic diseases. Besides their target cholesterol-lowering effects, statins also tend to appease patients' systemic inflammation levels. Now, Vieira-Silva and colleagues have identified an additional potential beneficial effect of statin therapy on the gut microbiota. In obese individuals, the prevalence of the dysbiotic Bact2 enterotype was significantly lower in those taking statins (6%) than in their non-treated counterparts (19%) - comparable to levels observed in non-obese participants (4%)...
Sara Vieira-Silva says, "These results suggest statins could potentially modulate the harmful gut microbiota alterations sustaining inflammation in obesity. Several interpretations of our results remain possible. On one hand, by appeasing gut inflammation, statin therapy might contribute to a less hostile gut environment, allowing the development of a healthy microbiota. On the other hand, a direct impact of statins on bacterial growth has been previously demonstrated, which could possibly benefit non-inflammatory bacteria and underlie anti-inflammatory effects of statin therapy."...
https://medicalxpress.com/news/2020-05-obesity-linked-gut-microbiota-disturbance...
-----------------------------------------------------------------------------------
Statin therapy is associated with lower prevalence of gut microbiota dysbiosis, Nature (2020). DOI: 10.1038/s41586-020-2269-x , www.nature.com/articles/s41586-020-2269-x
Abstract
Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease. Reported changes in stool consistency and inflammation status during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.
70margd
Salt: in mice, "a new gut–brain axis linking dietary habits to cognitive impairment through a gut-initiated adaptive immune response"
A New Connection between the Gut and Brain
A surprising way that diet leads risks of stroke and cognitive impairment
Jonathan D. Grinstein | December 5, 2018
...The researchers used mice, and found that immune responses in the small intestines set off a cascade of chemical responses reaching the brain’s blood vessels, reducing blood flow to the cortex and hippocampus, two brain regions crucial for learning and memory. This, in turn, brought a decline in tests of cognitive performance. The impairment in learning and memory was clear even in the absence of high blood pressure; they observed that the gut is reacting to the salt overload and directing immune signals that lay the basis for deterioration throughout the brain’s vital vascular complex and compromise cognitive function. While this study has only been carried out on research animals so far, the scientists believe it's likely that much of the same applies to people.
Lowering salt intake has been shown to have beneficial effects to overall health, so the researchers wanted to know whether these effects extend to this newly identified signaling cascade that begins in the gut and targets the brain’s blood vessels to, ultimately, affect cognitive function. When the mice were returned to a normal diet after being on a high salt diet, the detrimental health effects caused by excess salt intake were erased. A pharmacological intervention that disrupted the immune signals also reversed the effects.
The implications of this newly identified gut–brain connection extend to several autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease, that have been shown to activate the same immune signaling pathway implicated in this study. These autoimmune disorders have a high stroke risk and are linked to poorly functioning blood vessels in the nervous system...
https://www.scientificamerican.com/article/a-new-connection-between-the-gut-and-...
______________________________________________________
Giuseppe Faraco et al. 2018. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nature Neuroscience volume 21, pages240–249 (Jan 15, 2018) https://www.nature.com/articles/s41593-017-0059-z#Sec12
Abstract
A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia, but it remains unclear how dietary salt harms the brain. We report that, in mice, excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment. The effect depends on expansion of TH17 cells in the small intestine, resulting in a marked increase in plasma interleukin-17 (IL-17). Circulating IL-17, in turn, promotes endothelial dysfunction and cognitive impairment by the Rho kinase–dependent inhibitory phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide production in cerebral endothelial cells. The findings reveal a new gut–brain axis linking dietary habits to cognitive impairment through a gut-initiated adaptive immune response compromising brain function via circulating IL-17. Thus, the TH17 cell–IL-17 pathway is a putative target to counter the deleterious brain effects induced by dietary salt and other diseases associated with TH17 polarization.
______________________________________________________
Hmm, beet (juice) nitrates are converted by body to nitric oxide... https://www.webmd.com/food-recipes/features/truth-about-beetroot-juice
I like lemon powder on my popcorn...
Mohammed A. Shaik & Elizabeth M. C. Hillman. 2018. Skip the salt: your brain might thank you.
Nature Neuroscience volume 21, pages154–155 (Jan 25, 2018) https://www.nature.com/articles/s41593-018-0068-6
Excessive dietary salt can impair cerebral blood flow regulation, resulting in cognitive dysfunction in mice. A ‘gut–brain’ pathway is implicated that links expansion of TH17 lymphocytes in small intestine to elevated bloodstream interleukin-17, which impairs brain perfusion by decreasing nitric oxide production in brain vascular endothelium.
A New Connection between the Gut and Brain
A surprising way that diet leads risks of stroke and cognitive impairment
Jonathan D. Grinstein | December 5, 2018
...The researchers used mice, and found that immune responses in the small intestines set off a cascade of chemical responses reaching the brain’s blood vessels, reducing blood flow to the cortex and hippocampus, two brain regions crucial for learning and memory. This, in turn, brought a decline in tests of cognitive performance. The impairment in learning and memory was clear even in the absence of high blood pressure; they observed that the gut is reacting to the salt overload and directing immune signals that lay the basis for deterioration throughout the brain’s vital vascular complex and compromise cognitive function. While this study has only been carried out on research animals so far, the scientists believe it's likely that much of the same applies to people.
Lowering salt intake has been shown to have beneficial effects to overall health, so the researchers wanted to know whether these effects extend to this newly identified signaling cascade that begins in the gut and targets the brain’s blood vessels to, ultimately, affect cognitive function. When the mice were returned to a normal diet after being on a high salt diet, the detrimental health effects caused by excess salt intake were erased. A pharmacological intervention that disrupted the immune signals also reversed the effects.
The implications of this newly identified gut–brain connection extend to several autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease, that have been shown to activate the same immune signaling pathway implicated in this study. These autoimmune disorders have a high stroke risk and are linked to poorly functioning blood vessels in the nervous system...
https://www.scientificamerican.com/article/a-new-connection-between-the-gut-and-...
______________________________________________________
Giuseppe Faraco et al. 2018. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nature Neuroscience volume 21, pages240–249 (Jan 15, 2018) https://www.nature.com/articles/s41593-017-0059-z#Sec12
Abstract
A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia, but it remains unclear how dietary salt harms the brain. We report that, in mice, excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment. The effect depends on expansion of TH17 cells in the small intestine, resulting in a marked increase in plasma interleukin-17 (IL-17). Circulating IL-17, in turn, promotes endothelial dysfunction and cognitive impairment by the Rho kinase–dependent inhibitory phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide production in cerebral endothelial cells. The findings reveal a new gut–brain axis linking dietary habits to cognitive impairment through a gut-initiated adaptive immune response compromising brain function via circulating IL-17. Thus, the TH17 cell–IL-17 pathway is a putative target to counter the deleterious brain effects induced by dietary salt and other diseases associated with TH17 polarization.
______________________________________________________
Hmm, beet (juice) nitrates are converted by body to nitric oxide... https://www.webmd.com/food-recipes/features/truth-about-beetroot-juice
I like lemon powder on my popcorn...
Mohammed A. Shaik & Elizabeth M. C. Hillman. 2018. Skip the salt: your brain might thank you.
Nature Neuroscience volume 21, pages154–155 (Jan 25, 2018) https://www.nature.com/articles/s41593-018-0068-6
Excessive dietary salt can impair cerebral blood flow regulation, resulting in cognitive dysfunction in mice. A ‘gut–brain’ pathway is implicated that links expansion of TH17 lymphocytes in small intestine to elevated bloodstream interleukin-17, which impairs brain perfusion by decreasing nitric oxide production in brain vascular endothelium.
71margd
Microbiome associated with ALS, frontotemporal dementia...
ALS and gut bacteria linked in “remarkable” new Harvard study
Rich Haridy | May 13, 2020
...“Our study focused on the most commonly mutated gene in patients with ALS," says Kevin Eggan, corresponding author on the new study and professor of stem cell and regenerative biology at Harvard. "We made the remarkable discovery that the same mouse model – with identical genetics – had substantially different health outcomes at our different lab facilities. We traced the different outcomes to distinct gut microbial communities in these mice, and now have an intriguing hypothesis for why some individuals carrying this mutation develop ALS while others do not.”
https://newatlas.com/science/als-gut-bacteria-microbiome-harvard-study/
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Gut microbes tune inflammation and lifespan in a mouse model of amyotrophic lateral sclerosis
There is growing evidence that gut microbes can influence disease. Analysis of a mouse model of the neurodegenerative condition amyotrophic lateral sclerosis offers insight into how gut bacteria might contribute to this illness.
Ping Fang & Elaine Y. Hsiao | 13 May 2020
Animals have co-evolved with diverse communities of microorganisms that are integral to the development and activity of their immune and nervous systems. Alterations in the composition and function of the community of gut microorganisms (termed the microbiota) are increasingly being implicated in neurological disorders that involve neuroinflammation, including multiple sclerosis, autism spectrum disorder and Parkinson’s disease. Studies are also emerging that link the gut microbiota to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by the progressive loss of motor neurons crucial for movement, speech and cognition. This devastating disease is usually fatal within a few years of diagnosis. Writing in Nature, Burberry et al. fill some gaps in our knowledge of how gut microbes might contribute to ALS, from studies of the condition in a mouse model. Their findings might help to shed light on how a gene linked to ALS called C9orf72 affects this disease.
Initial studies have shown that the gut microbiota of people who have ALS differ from those of unaffected individuals. A study of a mouse model of the disease, based on an ALS-associated mutation in the Sod1 gene6, has provided strong evidence that alterations in the microbiota can exacerbate neurodegeneration and drive early mortality. That study also identified microbes and microbial molecules that promote improved motor function and longer lifespan in the mice. It showed that the particular positive or negative effects observed might depend on differences in the microbes encountered in the animals’ housing facility (termed a vivarium). Mouse models of inflammatory diseases have also revealed that the animals’ environment has such an effect...
https://www.nature.com/articles/d41586-020-01335-3
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Aaron Burberry et al. 2020. C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature (May 13, 2020) https://www.nature.com/articles/s41586-020-2288-7
Abstract
A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3,4,5,6,7,8,9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6,7,8,9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics—as well as transplanting gut microflora from a protective environment—attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.
----------------------------------------------------------
ALS and gut bacteria linked in “remarkable” new Harvard study
Rich Haridy | May 13, 2020
...“Our study focused on the most commonly mutated gene in patients with ALS," says Kevin Eggan, corresponding author on the new study and professor of stem cell and regenerative biology at Harvard. "We made the remarkable discovery that the same mouse model – with identical genetics – had substantially different health outcomes at our different lab facilities. We traced the different outcomes to distinct gut microbial communities in these mice, and now have an intriguing hypothesis for why some individuals carrying this mutation develop ALS while others do not.”
https://newatlas.com/science/als-gut-bacteria-microbiome-harvard-study/
------------------------------------------------------------
Gut microbes tune inflammation and lifespan in a mouse model of amyotrophic lateral sclerosis
There is growing evidence that gut microbes can influence disease. Analysis of a mouse model of the neurodegenerative condition amyotrophic lateral sclerosis offers insight into how gut bacteria might contribute to this illness.
Ping Fang & Elaine Y. Hsiao | 13 May 2020
Animals have co-evolved with diverse communities of microorganisms that are integral to the development and activity of their immune and nervous systems. Alterations in the composition and function of the community of gut microorganisms (termed the microbiota) are increasingly being implicated in neurological disorders that involve neuroinflammation, including multiple sclerosis, autism spectrum disorder and Parkinson’s disease. Studies are also emerging that link the gut microbiota to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by the progressive loss of motor neurons crucial for movement, speech and cognition. This devastating disease is usually fatal within a few years of diagnosis. Writing in Nature, Burberry et al. fill some gaps in our knowledge of how gut microbes might contribute to ALS, from studies of the condition in a mouse model. Their findings might help to shed light on how a gene linked to ALS called C9orf72 affects this disease.
Initial studies have shown that the gut microbiota of people who have ALS differ from those of unaffected individuals. A study of a mouse model of the disease, based on an ALS-associated mutation in the Sod1 gene6, has provided strong evidence that alterations in the microbiota can exacerbate neurodegeneration and drive early mortality. That study also identified microbes and microbial molecules that promote improved motor function and longer lifespan in the mice. It showed that the particular positive or negative effects observed might depend on differences in the microbes encountered in the animals’ housing facility (termed a vivarium). Mouse models of inflammatory diseases have also revealed that the animals’ environment has such an effect...
https://www.nature.com/articles/d41586-020-01335-3
------------------------------------------------------------
Aaron Burberry et al. 2020. C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature (May 13, 2020) https://www.nature.com/articles/s41586-020-2288-7
Abstract
A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3,4,5,6,7,8,9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6,7,8,9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics—as well as transplanting gut microflora from a protective environment—attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.
----------------------------------------------------------
72margd
Gut microbiota associated with ketogenic diets reduces the levels of intestinal pro-inflammatory Th17 cells, a type of T cell critical for fighting off infectious disease, but also known to promote inflammation in autoimmune diseases.
Ketogenic diets alter gut microbiome in humans, mice
University of California, San Francisco | May 20, 2020
..."ketone bodies," a molecular byproduct that gives the ketogenic diet its name, directly impact the gut microbiome in ways that may ultimately suppress inflammation, suggesting evidence for potential benefits of ketone bodies as a therapy for autoimmune disorders affecting the gut.
...shifting between standard and ketogenic diets dramatically changed the proportions of common gut microbial phyla Actinobacteria, Bacteroidetes, and Firmicutes in participants' guts, including significant changes in 19 different bacterial genera...the common probiotic Bifidobacteria—which showed the greatest decrease on the ketogenic diet.
...as animals' diets were shifted from a standard diet towards stricter carbohydrate restriction, their microbes also began shifting, correlated with a gradual rise in ketone bodies.
"This was a little surprising to me," (Peter Turnbaugh, Ph.D., a UCSF associate professor of microbiology and immunology, member of the UCSF Benioff Center for Microbiome Medicine and a Chan Zuckerberg Biohub Investigator) said. "As someone who is new to the keto field, I had assumed that producing ketone bodies was an all-or-nothing effect once you got to a low enough level of carb intake. But this suggests that you may get some of the effects of ketosis quite quickly."
...even in mice who were eating normal amounts of carbohydrates, the mere presence of added ketones was enough to produce many of the specific microbial changes seen in the ketogenic diet.
"This is a really fascinating finding because it suggests that the effects of ketogenic diets on the microbiome are not just about the diet itself, but how the diet alters the body's metabolism, which then has downstream effects on the microbiome," Turnbaugh said. "For many people, maintaining a strict low-carbohydrate or ketogenic diet is extremely challenging, but if future studies find that there are health benefits from the microbial shifts caused by ketone bodies themselves, that could make for a much more palatable therapeutic approach."
__________________________________________
Qi Yan Ang et al. 2020. Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Cell. May 20, 2020DOI:https://doi.org/10.1016/j.cell.2020.04.027 https://www.cell.com/cell/pdf/S0092-8674(20)30490-6.pdf
Highlights
• Ketogenic diets (KDs) alter the gut microbiota in a manner distinct from high-fat diets
• Gut microbial shifts on KDs are driven in part through host production of ketone bodies
• β-hydroxybutyrate selectively inhibits bifidobacterial growth
• The KD-associated gut microbiota reduces levels of intestinal Th17 cells
Summary
Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.
Ketogenic diets alter gut microbiome in humans, mice
University of California, San Francisco | May 20, 2020
..."ketone bodies," a molecular byproduct that gives the ketogenic diet its name, directly impact the gut microbiome in ways that may ultimately suppress inflammation, suggesting evidence for potential benefits of ketone bodies as a therapy for autoimmune disorders affecting the gut.
...shifting between standard and ketogenic diets dramatically changed the proportions of common gut microbial phyla Actinobacteria, Bacteroidetes, and Firmicutes in participants' guts, including significant changes in 19 different bacterial genera...the common probiotic Bifidobacteria—which showed the greatest decrease on the ketogenic diet.
...as animals' diets were shifted from a standard diet towards stricter carbohydrate restriction, their microbes also began shifting, correlated with a gradual rise in ketone bodies.
"This was a little surprising to me," (Peter Turnbaugh, Ph.D., a UCSF associate professor of microbiology and immunology, member of the UCSF Benioff Center for Microbiome Medicine and a Chan Zuckerberg Biohub Investigator) said. "As someone who is new to the keto field, I had assumed that producing ketone bodies was an all-or-nothing effect once you got to a low enough level of carb intake. But this suggests that you may get some of the effects of ketosis quite quickly."
...even in mice who were eating normal amounts of carbohydrates, the mere presence of added ketones was enough to produce many of the specific microbial changes seen in the ketogenic diet.
"This is a really fascinating finding because it suggests that the effects of ketogenic diets on the microbiome are not just about the diet itself, but how the diet alters the body's metabolism, which then has downstream effects on the microbiome," Turnbaugh said. "For many people, maintaining a strict low-carbohydrate or ketogenic diet is extremely challenging, but if future studies find that there are health benefits from the microbial shifts caused by ketone bodies themselves, that could make for a much more palatable therapeutic approach."
__________________________________________
Qi Yan Ang et al. 2020. Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Cell. May 20, 2020DOI:https://doi.org/10.1016/j.cell.2020.04.027 https://www.cell.com/cell/pdf/S0092-8674(20)30490-6.pdf
Highlights
• Ketogenic diets (KDs) alter the gut microbiota in a manner distinct from high-fat diets
• Gut microbial shifts on KDs are driven in part through host production of ketone bodies
• β-hydroxybutyrate selectively inhibits bifidobacterial growth
• The KD-associated gut microbiota reduces levels of intestinal Th17 cells
Summary
Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.
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Brown, white and beige: understanding your body’s different fat cells could help with weight loss
Trust Diya | May 18, 2020
...Beige fat cells are derived from white fat in a process called “browning” which is triggered by exposure to low temperatures, typically 3°C above a person’s shivering temperature point, which is around 11°C for women and around 9°C for men.
Other stimuli such as good nutrition and exercise are also believed to encourage the browning process.
...Nutritional supplements, such as the flavonoids resveratrol and quercetin, which are found in fruits and vegetables, can help the browning process. Exercise has also been shown to increase browning.
Exposure to temperatures slightly above the shivering point for at least two hours is also known to help with browning. However, this needs to be practised regularly to see any real changes.
Studies also show that brown fat cells are associated with better health. They encourage weight loss, which may subsequently reduce obesity and other related diseases caused by excess weight.
Brown fat cells also reduce the risk of hypothermia and can reduce the risk of diabetes by increasing insulin sensitivity. The ability to cause the browning of white fat cells and turn them into beige cells therefore brings the potential for better health.
https://theconversation.com/brown-white-and-beige-understanding-your-bodys-diffe...
Trust Diya | May 18, 2020
...Beige fat cells are derived from white fat in a process called “browning” which is triggered by exposure to low temperatures, typically 3°C above a person’s shivering temperature point, which is around 11°C for women and around 9°C for men.
Other stimuli such as good nutrition and exercise are also believed to encourage the browning process.
...Nutritional supplements, such as the flavonoids resveratrol and quercetin, which are found in fruits and vegetables, can help the browning process. Exercise has also been shown to increase browning.
Exposure to temperatures slightly above the shivering point for at least two hours is also known to help with browning. However, this needs to be practised regularly to see any real changes.
Studies also show that brown fat cells are associated with better health. They encourage weight loss, which may subsequently reduce obesity and other related diseases caused by excess weight.
Brown fat cells also reduce the risk of hypothermia and can reduce the risk of diabetes by increasing insulin sensitivity. The ability to cause the browning of white fat cells and turn them into beige cells therefore brings the potential for better health.
https://theconversation.com/brown-white-and-beige-understanding-your-bodys-diffe...
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I think I remember my Dad had a white oil paint that contained titanium dioxide. Not sure if I read it in food label, but no doubt it was in something I ate over the years... Nanoparticles... :(
Common food additive alters gut microbiota in mice
Emily Henderson, B.Sc. | Jun 25 2020
...Human exposure to foodborne TiO2 NPs (nanoparticles) comes primarily from a food additive known as E171, which is made up of different-size particles of TiO2, including one-third or more that are nanoscale. E171, which makes products look whiter and more opaque, is found in such food as desserts, candy, beverages and gum. E171 exposure is two to four times higher in U.S. children than in adults...
..."In both the non-obese mice and obese mice, the gut microbiota was disturbed by both E171 and TiO2 NPs," Xiao says. "The nanosized particles caused more negative changes in both groups of mice." Moreover, the obese mice were more susceptible to the adverse effects of TiO2 NPs, causing more damage in obese mice than in non-obese ones.
...TiO2 NPs decreased cecal levels of short-chain fatty acids, which are essential for colon health, and increased pro-inflammatory immune cells and cytokines in the colon, indicating an inflammatory state.
https://www.news-medical.net/news/20200625/Common-food-additive-alters-gut-micro...
________________________________________
Cao, X., et al. (2020) Foodborne Titanium Dioxide Nanoparticles Induce Stronger Adverse Effects in Obese Mice than Non‐Obese Mice: Gut Microbiota Dysbiosis, Colonic Inflammation, and Proteome Alterations. Small. doi.org/10.1002/smll.202001858. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202001858
Abstract
The recent ban of titanium dioxide (TiO2) as a food additive (E171) in France intensified the controversy on safety of foodborne‐TiO2 nanoparticles (NPs). This study determines the biological effects of TiO2 NPs and TiO2 (E171) in obese and non‐obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO2 (E171, 112 nm) and TiO2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short‐chain fatty acids. Both TiO2 (E171) and TiO2 NPs increase abundance of pro‐inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO2 NPs cause stronger colonic inflammation than TiO2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non‐obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.
Common food additive alters gut microbiota in mice
Emily Henderson, B.Sc. | Jun 25 2020
...Human exposure to foodborne TiO2 NPs (nanoparticles) comes primarily from a food additive known as E171, which is made up of different-size particles of TiO2, including one-third or more that are nanoscale. E171, which makes products look whiter and more opaque, is found in such food as desserts, candy, beverages and gum. E171 exposure is two to four times higher in U.S. children than in adults...
..."In both the non-obese mice and obese mice, the gut microbiota was disturbed by both E171 and TiO2 NPs," Xiao says. "The nanosized particles caused more negative changes in both groups of mice." Moreover, the obese mice were more susceptible to the adverse effects of TiO2 NPs, causing more damage in obese mice than in non-obese ones.
...TiO2 NPs decreased cecal levels of short-chain fatty acids, which are essential for colon health, and increased pro-inflammatory immune cells and cytokines in the colon, indicating an inflammatory state.
https://www.news-medical.net/news/20200625/Common-food-additive-alters-gut-micro...
________________________________________
Cao, X., et al. (2020) Foodborne Titanium Dioxide Nanoparticles Induce Stronger Adverse Effects in Obese Mice than Non‐Obese Mice: Gut Microbiota Dysbiosis, Colonic Inflammation, and Proteome Alterations. Small. doi.org/10.1002/smll.202001858. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202001858
Abstract
The recent ban of titanium dioxide (TiO2) as a food additive (E171) in France intensified the controversy on safety of foodborne‐TiO2 nanoparticles (NPs). This study determines the biological effects of TiO2 NPs and TiO2 (E171) in obese and non‐obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO2 (E171, 112 nm) and TiO2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short‐chain fatty acids. Both TiO2 (E171) and TiO2 NPs increase abundance of pro‐inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO2 NPs cause stronger colonic inflammation than TiO2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non‐obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.
75margd
Okinawa Institute of Science and Technology (OIST) Graduate University. "Fasting ramps up human metabolism, study shows." ScienceDaily. ScienceDaily, 31 January 2019. www.sciencedaily.com/releases/2019/01/190131113934.htm
...an analysis of whole human blood, plasma, and red blood cells drawn from four fasting individuals. The researchers monitored changing levels of metabolites -- substances formed during the chemical processes that grant organisms energy and allow them to grow. The results revealed 44 metabolites, including 30 that were previously unrecognized, that increased universally among subjects between 1.5- to 60-fold within just 58 hours of fasting.
In previous research, the G0 Cell Unit identified various metabolites whose quantities decline with age, including three known as leucine, isoleucine, and ophthalmic acid. In fasting individuals, these metabolites increase in level, suggesting a mechanism by which fasting could help increase longevity...
Metabolites Give Clues to Mechanism and Health Effects
The human body tends to utilize carbohydrates for quick energy -- when they're available. When starved of carbs, the body begins looting its alternate energy stores. The act of "energy substitution" leaves a trail of evidence, namely metabolites known as butyrates, carnitines, and branched-chain amino acids. These well-known markers of energy substitution have been shown to accumulate during fasting.
But fasting appears to elicit effects far beyond energy substitution. In their comprehensive analysis of human blood, the researchers noted both established fasting markers and many more. For example, they found a global increase in substances produced by the citric acid cycle, a process by which organisms release energy stored in the chemical bonds of carbohydrates, proteins and lipids. The marked increase suggests that, during fasting, the tiny powerhouses running every cell are thrown into overdrive.
Fasting also appeared to enhance the metabolism of purine and pyrimidine, chemical substances which play key roles in gene expression and protein synthesis. The finding suggests fasting may reprogram which proteins cells build at what time, thus altering their function. The change may promote homeostasis in cells, or serve to edit their gene expression in response to environmental influences.
When metabolized, purine and pyrimidine also boost the body's production of antioxidants. Several antioxidants, such as ergothioneine and carnosine, were found to increase significantly over the 58-hour study period. Antioxidants serve to protect cells from free radicals produced during metabolism. Products of a metabolic pathway called the "pentose phosphate pathway" also stay the harmful effects of oxidation, and were similarly seen to increase during fasting, but only in plasma.
Newfound Health Benefits of Fasting?
The authors suggest that these antioxidative effects may stand as the body's principal response to fasting, as starvation can foster a dangerously oxidative internal environment. Their exploratory study provides the first evidence of antioxidants as a fasting marker. In addition, the study introduces the novel notion that fasting might boost production of several age-related metabolites, abundant in young people, but depleted in old.
"Recent aging studies have shown that caloric restriction and fasting have a prolonging effect on lifespan in model animals...but the detailed mechanism has remained a mystery," said Teruya. "It might be possible to verify the anti-aging effect from various viewpoints by developing exercise programs or drugs capable of causing the metabolic reaction similar to fasting."
The findings expand on established ideas of what fasting could do for human health. The next step would be to replicate these results in a larger study, or investigate how the metabolic changes might be triggered by other means...
-------------------------------------------------------------
Takayuki Teruya, Romanas Chaleckis, Junko Takada, Mitsuhiro Yanagida, Hiroshi Kondoh. Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood. Scientific Reports, 2019; 9 (1) DOI: 10.1038/s41598-018-36674-9 https://www.nature.com/articles/s41598-018-36674-9
Abstract
During human fasting, metabolic markers, including butyrates, carnitines, and branched-chain amino acids, are upregulated for energy substitution through gluconeogenesis and use of stored lipids. We performed non-targeted, accurate semiquantitative metabolomic analysis of human whole blood, plasma, and red blood cells during 34–58 hr fasting of four volunteers. During this period, 44 of ~130 metabolites increased 1.5~60-fold. Consistently fourteen were previously reported. However, we identified another 30 elevated metabolites, implicating hitherto unrecognized metabolic mechanisms induced by fasting. Metabolites in pentose phosphate pathway are abundant, probably due to demand for antioxidants, NADPH, gluconeogenesis and anabolic metabolism. Global increases of TCA cycle-related compounds reflect enhanced mitochondrial activity in tissues during fasting. Enhanced purine/pyrimidine metabolites support RNA/protein synthesis and transcriptional reprogramming, which is promoted also by some fasting-related metabolites, possibly via epigenetic modulations. Thus diverse, pronounced metabolite increases result from greatly activated catabolism and anabolism stimulated by fasting. Anti-oxidation may be a principal response to fasting.
...an analysis of whole human blood, plasma, and red blood cells drawn from four fasting individuals. The researchers monitored changing levels of metabolites -- substances formed during the chemical processes that grant organisms energy and allow them to grow. The results revealed 44 metabolites, including 30 that were previously unrecognized, that increased universally among subjects between 1.5- to 60-fold within just 58 hours of fasting.
In previous research, the G0 Cell Unit identified various metabolites whose quantities decline with age, including three known as leucine, isoleucine, and ophthalmic acid. In fasting individuals, these metabolites increase in level, suggesting a mechanism by which fasting could help increase longevity...
Metabolites Give Clues to Mechanism and Health Effects
The human body tends to utilize carbohydrates for quick energy -- when they're available. When starved of carbs, the body begins looting its alternate energy stores. The act of "energy substitution" leaves a trail of evidence, namely metabolites known as butyrates, carnitines, and branched-chain amino acids. These well-known markers of energy substitution have been shown to accumulate during fasting.
But fasting appears to elicit effects far beyond energy substitution. In their comprehensive analysis of human blood, the researchers noted both established fasting markers and many more. For example, they found a global increase in substances produced by the citric acid cycle, a process by which organisms release energy stored in the chemical bonds of carbohydrates, proteins and lipids. The marked increase suggests that, during fasting, the tiny powerhouses running every cell are thrown into overdrive.
Fasting also appeared to enhance the metabolism of purine and pyrimidine, chemical substances which play key roles in gene expression and protein synthesis. The finding suggests fasting may reprogram which proteins cells build at what time, thus altering their function. The change may promote homeostasis in cells, or serve to edit their gene expression in response to environmental influences.
When metabolized, purine and pyrimidine also boost the body's production of antioxidants. Several antioxidants, such as ergothioneine and carnosine, were found to increase significantly over the 58-hour study period. Antioxidants serve to protect cells from free radicals produced during metabolism. Products of a metabolic pathway called the "pentose phosphate pathway" also stay the harmful effects of oxidation, and were similarly seen to increase during fasting, but only in plasma.
Newfound Health Benefits of Fasting?
The authors suggest that these antioxidative effects may stand as the body's principal response to fasting, as starvation can foster a dangerously oxidative internal environment. Their exploratory study provides the first evidence of antioxidants as a fasting marker. In addition, the study introduces the novel notion that fasting might boost production of several age-related metabolites, abundant in young people, but depleted in old.
"Recent aging studies have shown that caloric restriction and fasting have a prolonging effect on lifespan in model animals...but the detailed mechanism has remained a mystery," said Teruya. "It might be possible to verify the anti-aging effect from various viewpoints by developing exercise programs or drugs capable of causing the metabolic reaction similar to fasting."
The findings expand on established ideas of what fasting could do for human health. The next step would be to replicate these results in a larger study, or investigate how the metabolic changes might be triggered by other means...
-------------------------------------------------------------
Takayuki Teruya, Romanas Chaleckis, Junko Takada, Mitsuhiro Yanagida, Hiroshi Kondoh. Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood. Scientific Reports, 2019; 9 (1) DOI: 10.1038/s41598-018-36674-9 https://www.nature.com/articles/s41598-018-36674-9
Abstract
During human fasting, metabolic markers, including butyrates, carnitines, and branched-chain amino acids, are upregulated for energy substitution through gluconeogenesis and use of stored lipids. We performed non-targeted, accurate semiquantitative metabolomic analysis of human whole blood, plasma, and red blood cells during 34–58 hr fasting of four volunteers. During this period, 44 of ~130 metabolites increased 1.5~60-fold. Consistently fourteen were previously reported. However, we identified another 30 elevated metabolites, implicating hitherto unrecognized metabolic mechanisms induced by fasting. Metabolites in pentose phosphate pathway are abundant, probably due to demand for antioxidants, NADPH, gluconeogenesis and anabolic metabolism. Global increases of TCA cycle-related compounds reflect enhanced mitochondrial activity in tissues during fasting. Enhanced purine/pyrimidine metabolites support RNA/protein synthesis and transcriptional reprogramming, which is promoted also by some fasting-related metabolites, possibly via epigenetic modulations. Thus diverse, pronounced metabolite increases result from greatly activated catabolism and anabolism stimulated by fasting. Anti-oxidation may be a principal response to fasting.
76margd
A Chinese study reversed Type 2 diabetes with a LOT of dietary fiber (~50 mg? including inulin). I'll provide reference again if I can find it. New study below might show how?
Science Magazine: A gut microbiota-modulated neural pathway linking the lower intestines to the liver and pancreas autonomously regulates blood glucose, researchers report in Science, which could have implications for some metabolic disorder treatments.
Paul A. Muller et al. 2020. Microbiota-modulated CART+ enteric neurons autonomously regulate blood glucose. Science 27 Aug 2020: eabd6176. DOI: 10.1126/science.abd6176 https://science.sciencemag.org/content/early/2020/08/26/science.abd6176
Abstract
The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEAN) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially-responsive subset of viscerofugal CART+ neurons, enriched in the ileum and colon, modulated feeding and glucose metabolism. These CART+ neurons send axons to the prevertebral ganglia and are poly-synaptically connected to the liver and pancreas. Microbiota depletion led to NLRP6– and Caspase 11-dependent loss of CART+ neurons, and impaired glucose regulation. Hence, iEAN subsets appear to be capable of regulating blood glucose levels independently from the central nervous system.
Science Magazine: A gut microbiota-modulated neural pathway linking the lower intestines to the liver and pancreas autonomously regulates blood glucose, researchers report in Science, which could have implications for some metabolic disorder treatments.
Paul A. Muller et al. 2020. Microbiota-modulated CART+ enteric neurons autonomously regulate blood glucose. Science 27 Aug 2020: eabd6176. DOI: 10.1126/science.abd6176 https://science.sciencemag.org/content/early/2020/08/26/science.abd6176
Abstract
The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEAN) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially-responsive subset of viscerofugal CART+ neurons, enriched in the ileum and colon, modulated feeding and glucose metabolism. These CART+ neurons send axons to the prevertebral ganglia and are poly-synaptically connected to the liver and pancreas. Microbiota depletion led to NLRP6– and Caspase 11-dependent loss of CART+ neurons, and impaired glucose regulation. Hence, iEAN subsets appear to be capable of regulating blood glucose levels independently from the central nervous system.
77margd
The key to minimizing health risks associated with aging
The Westmead Institute for Medical Research | September 11, 2020
...(WIMR's Associate Professor Dr. Kedar Ghimire), who conceptualized and conducted the study, found the answer. "In older mice, we observed that endothelial cells that form the inner lining of arteries showed signs of exhaustion, including decreased proliferation, migration and tube formation. However, when the same cells were devoid of CD47, they did not show signs of this deterioration. We also treated the arteries of older people with a CD47 blocking antibody and observed the same effects," says Dr. Ghimire.
This study indicates that CD47 increases during aging and facilitates the dysfunction of arteries and metabolic balance. If this protein is not allowed to function during aging, many of these health issues can be minimized.
(WIMR's) Associate Professor (Natasha) Rogers says, "...Our findings provide a strong indication that a therapy to target CD47 could minimize some of these serious dysfunctions associated with aging."
Dr. Ghimire says, '"As a next step, we plan to study the consequences of increased CD47 in human metabolism and hope to unravel the effects of CD47 in diabetes."
https://medicalxpress.com/news/2020-09-key-minimizing-health-aging.html
-----------------------------------------------------------------------------------------------
Kedar Ghimire et al. 2020. CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis. Cells July 15, 2020, 9(7), 1695; https://doi.org/10.3390/cells9071695. https://www.mdpi.com/2073-4409/9/7/1695
Abstract
...we identify cell surface receptor CD47 as a novel age-sensitive driver of vascular and metabolic dysfunction...aged CD47-null mice were resistant to age- and diet-associated weight gain, glucose intolerance and insulin desensitization...Our findings provide a strong rationale for therapeutically targeting CD47 to minimize these dysfunctions during aging...
The Westmead Institute for Medical Research | September 11, 2020
...(WIMR's Associate Professor Dr. Kedar Ghimire), who conceptualized and conducted the study, found the answer. "In older mice, we observed that endothelial cells that form the inner lining of arteries showed signs of exhaustion, including decreased proliferation, migration and tube formation. However, when the same cells were devoid of CD47, they did not show signs of this deterioration. We also treated the arteries of older people with a CD47 blocking antibody and observed the same effects," says Dr. Ghimire.
This study indicates that CD47 increases during aging and facilitates the dysfunction of arteries and metabolic balance. If this protein is not allowed to function during aging, many of these health issues can be minimized.
(WIMR's) Associate Professor (Natasha) Rogers says, "...Our findings provide a strong indication that a therapy to target CD47 could minimize some of these serious dysfunctions associated with aging."
Dr. Ghimire says, '"As a next step, we plan to study the consequences of increased CD47 in human metabolism and hope to unravel the effects of CD47 in diabetes."
https://medicalxpress.com/news/2020-09-key-minimizing-health-aging.html
-----------------------------------------------------------------------------------------------
Kedar Ghimire et al. 2020. CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis. Cells July 15, 2020, 9(7), 1695; https://doi.org/10.3390/cells9071695. https://www.mdpi.com/2073-4409/9/7/1695
Abstract
...we identify cell surface receptor CD47 as a novel age-sensitive driver of vascular and metabolic dysfunction...aged CD47-null mice were resistant to age- and diet-associated weight gain, glucose intolerance and insulin desensitization...Our findings provide a strong rationale for therapeutically targeting CD47 to minimize these dysfunctions during aging...
78margd
Only 2.5 h wearing water-perfused vests cooled to 14–17 °C (57.2-62.6F) effected the desired change.
Our thermostat is frequently set to 62F in day and lower at night (warmer in eve)--bet blankets and sweaters dull the effect...plus passive solar at work sometimes during the day...
Vitamin A boosts fat burning in cold conditions
The conversion of white into brown adipose tissue is a promising target for obesity treatment
Medical University of Vienna | October 21, 2020
Summary:
A recent study shows that cold ambient temperatures increase vitamin A levels in humans and mice. This helps convert 'bad' white adipose tissue into 'good' brown adipose tissue which stimulates fat burning and heat generation.
...moderate application of cold increases the levels of vitamin A and its blood transporter, retinol-binding protein, in humans and mice. Most of the vitamin A reserves are stored in the liver and cold exposure seems to stimulate the redistribution of vitamin A towards the adipose tissue. The cold-induced increase in vitamin A led to a conversion of white fat into brown fat ("browning"), with a higher rate of fat burning...
When (Florian Kiefer from the Division of Endocrinology and Metabolism, Department of Medicine III at MedUni Vienna) and his team blocked the vitamin A transporter "retinol-binding protein" in mice by genetic manipulation, both the cold-mediated rise in vitamin A and the "browning" of the white fat were blunted: "As a consequence, fat oxidation and heat production were perturbed so that the mice were no longer able to protect themselves against the cold," explains Kiefer. In contrast, the addition of vitamin A to human white fat cells led to the expression of brown fat cell characteristics, with increased metabolic activity and energy consumption.
"Our results show that vitamin A plays an important role in the function of adipose tissue and affects global energy metabolism. However, this is not an argument for consuming large amounts of vitamin A supplements if not prescribed, because it is critical that vitamin A is transported to the right cells at the right time," explains the MedUni Vienna researcher. "We have discovered a new mechanism by which vitamin A regulates lipid combustion and heat generation in cold conditions. This could help us to develop new therapeutic interventions that exploit this specific mechanism."
https://www.sciencedaily.com/releases/2020/10/201021112318.htm
---------------------------------------------------------
Anna Fenzl, Oana Cristina Kulterer, Katrin Spirk, Goran Mitulović, Rodrig Marculescu, Martin Bilban, Sabina Baumgartner-Parzer, Alexandra Kautzky-Willer, Lukas Kenner, Jorge Plutzky, Loredana Quadro, Florian W. Kiefer. Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis. Molecular Metabolism, 2020; 101088 DOI: 10.1016/j.molmet.2020.101088 https://www.sciencedirect.com/science/article/pii/S2212877820301629?via%3Dihub
Abstract
Objective
Transformation of white into brown fat (“browning”) reduces obesity in many preclinical models and holds great promise as a therapeutic concept in metabolic disease. Vitamin A metabolites (retinoids) have been linked to thermogenic programming of adipose tissue; however, the physiologic importance of systemic retinoid transport for adipose tissue browning and adaptive thermogenesis is unknown.
Methods
We performed cold exposure studies in mice and humans and used a genetic model of defective vitamin A transport, the retinol binding protein deficient (Rbp−/-) mouse, to study the effects of cooling on systemic vitamin A and the relevance of intact retinoid transport on cold-induced adipose tissue browning.
Results
We show that cold stimulation in mice and humans leads to an increase in circulating retinol and its plasma transporter, Rbp. In Rbp−/- mice, thermogenic programming of adipocytes and oxidative mitochondrial function are dramatically impaired in subcutaneous white fat, which renders Rbp−/- mice more cold-sensitive. In contrast, retinol stimulation in primary human adipocytes promotes thermogenic gene expression and mitochondrial respiration. In humans, cold-mediated retinol increase is associated with a shift in oxidative substrate metabolism suggestive of higher lipid utilisation.
Conclusions
Systemic vitamin A levels are regulated by cold exposure in mice and humans, and intact retinoid transport is essential for cold-induced adipose tissue browning and adaptive thermogenesis.
...Cold exposure (24 h at 4 °C) significantly increased circulating retinol and RBP concentrations in 129/Sv x C57BL/6J mice... Next, we tested whether cold-induced alterations in vitamin A metabolism were also present in humans. Thirty healthy lean subjects...were exposed to moderate cold (14–17 °C) for 2.5 h using water-perfused cooling vests under a protocol which has been used successfully to activate BAT in humans.... Notably, only 2.5 h of moderate cold exposure increased circulating retinol and RBP concentrations significantly in these lean subjects...
Our thermostat is frequently set to 62F in day and lower at night (warmer in eve)--bet blankets and sweaters dull the effect...plus passive solar at work sometimes during the day...
Vitamin A boosts fat burning in cold conditions
The conversion of white into brown adipose tissue is a promising target for obesity treatment
Medical University of Vienna | October 21, 2020
Summary:
A recent study shows that cold ambient temperatures increase vitamin A levels in humans and mice. This helps convert 'bad' white adipose tissue into 'good' brown adipose tissue which stimulates fat burning and heat generation.
...moderate application of cold increases the levels of vitamin A and its blood transporter, retinol-binding protein, in humans and mice. Most of the vitamin A reserves are stored in the liver and cold exposure seems to stimulate the redistribution of vitamin A towards the adipose tissue. The cold-induced increase in vitamin A led to a conversion of white fat into brown fat ("browning"), with a higher rate of fat burning...
When (Florian Kiefer from the Division of Endocrinology and Metabolism, Department of Medicine III at MedUni Vienna) and his team blocked the vitamin A transporter "retinol-binding protein" in mice by genetic manipulation, both the cold-mediated rise in vitamin A and the "browning" of the white fat were blunted: "As a consequence, fat oxidation and heat production were perturbed so that the mice were no longer able to protect themselves against the cold," explains Kiefer. In contrast, the addition of vitamin A to human white fat cells led to the expression of brown fat cell characteristics, with increased metabolic activity and energy consumption.
"Our results show that vitamin A plays an important role in the function of adipose tissue and affects global energy metabolism. However, this is not an argument for consuming large amounts of vitamin A supplements if not prescribed, because it is critical that vitamin A is transported to the right cells at the right time," explains the MedUni Vienna researcher. "We have discovered a new mechanism by which vitamin A regulates lipid combustion and heat generation in cold conditions. This could help us to develop new therapeutic interventions that exploit this specific mechanism."
https://www.sciencedaily.com/releases/2020/10/201021112318.htm
---------------------------------------------------------
Anna Fenzl, Oana Cristina Kulterer, Katrin Spirk, Goran Mitulović, Rodrig Marculescu, Martin Bilban, Sabina Baumgartner-Parzer, Alexandra Kautzky-Willer, Lukas Kenner, Jorge Plutzky, Loredana Quadro, Florian W. Kiefer. Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis. Molecular Metabolism, 2020; 101088 DOI: 10.1016/j.molmet.2020.101088 https://www.sciencedirect.com/science/article/pii/S2212877820301629?via%3Dihub
Abstract
Objective
Transformation of white into brown fat (“browning”) reduces obesity in many preclinical models and holds great promise as a therapeutic concept in metabolic disease. Vitamin A metabolites (retinoids) have been linked to thermogenic programming of adipose tissue; however, the physiologic importance of systemic retinoid transport for adipose tissue browning and adaptive thermogenesis is unknown.
Methods
We performed cold exposure studies in mice and humans and used a genetic model of defective vitamin A transport, the retinol binding protein deficient (Rbp−/-) mouse, to study the effects of cooling on systemic vitamin A and the relevance of intact retinoid transport on cold-induced adipose tissue browning.
Results
We show that cold stimulation in mice and humans leads to an increase in circulating retinol and its plasma transporter, Rbp. In Rbp−/- mice, thermogenic programming of adipocytes and oxidative mitochondrial function are dramatically impaired in subcutaneous white fat, which renders Rbp−/- mice more cold-sensitive. In contrast, retinol stimulation in primary human adipocytes promotes thermogenic gene expression and mitochondrial respiration. In humans, cold-mediated retinol increase is associated with a shift in oxidative substrate metabolism suggestive of higher lipid utilisation.
Conclusions
Systemic vitamin A levels are regulated by cold exposure in mice and humans, and intact retinoid transport is essential for cold-induced adipose tissue browning and adaptive thermogenesis.
...Cold exposure (24 h at 4 °C) significantly increased circulating retinol and RBP concentrations in 129/Sv x C57BL/6J mice... Next, we tested whether cold-induced alterations in vitamin A metabolism were also present in humans. Thirty healthy lean subjects...were exposed to moderate cold (14–17 °C) for 2.5 h using water-perfused cooling vests under a protocol which has been used successfully to activate BAT in humans.... Notably, only 2.5 h of moderate cold exposure increased circulating retinol and RBP concentrations significantly in these lean subjects...
79margd
Protein study reveals a powerful effect on fat-burning
Extra protein could give people a "metabolic advantage."
Inverse | Nov 27, 2020
...In the experiment, healthy people who ate high protein total diet replacement products burned more calories and fat over 32 hours, compared to people on a North American diet — a mix of various carbs, proteins, and fats. The protein group also ended the experiment burning more fat than they consumed, likely implying future weight loss over time.
The experiment also offers direct evidence that all calories aren't created equal.
"Our study proved that the same number of calories but from different diets can elicit different responses in energy metabolism," study co-authors Carla Prado and Camila Pinto (University of Alberta)....
While the study is limited to healthy people with a normal weight, scientists hope the findings will eventually lead to new interventions for people trying to manage a healthy weight — a step toward a longer life, free of disease.
...The team recruited a group of healthy, normal-weight adults between the ages of 18 and 35. Normal weight is defined as having a Body Mass Index between 18.5 and 24.9 kg/m.
Participants were then randomly split into one of two groups: one group was fed the high-protein total diet replacement, which consisted of 35 percent carbohydrate, 40 percent protein, and 25 percent fat. The product is a commercially available supplement comprised of soy protein, yogurt, and honey. (margd: I think original version of South Beach Diet aimed to keep carbs to 30% in 1st phase?)
The second group, or control group, was fed a diet with the same number of calories, but consisting of 55 percent carbohydrate, 15 percent protein, and 30 percent fat — what's considered a typical North American diet. Both groups received the prescribed diets for a 32-hour period while inside a metabolic chamber.
...On average, the high-protein total diet replacement, when compared to the North American diet, resulted in:
Higher energy expenditure
Increased fat oxidation
Negative fat balance, which implies body fat loss
"These results suggest that normal-weight individuals can have some metabolic advantages when consuming this type of nutritional product," the researchers explain.
It also suggests a higher proportion of protein might be beneficial compared to a diet consisting of the same number of calories, but with a lower proportion of protein...
https://www.inverse.com/mind-body/protein-weight-loss-study-explained
__________________________________________________________
Camila L P Oliveira et al. 2020. A high-protein total diet replacement increases energy expenditure and leads to negative fat balance in healthy, normal-weight adults. The American Journal of Clinical Nutrition (18 November 2020), https://doi.org/10.1093/ajcn/nqaa283 https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqaa283/5986961
ABSTRACT
Background
High-protein diets and total diet replacements are becoming increasingly popular for weight loss; however, further research is needed to elucidate their impact on the mechanisms involved in weight regulation.
Objective
The aim of this inpatient metabolic balance study was to compare the impact of a high-protein total diet replacement (HP-TDR) versus a control diet (CON) on select components of energy metabolism in healthy adults of both sexes.
Methods
The acute intervention was a randomized, controlled, crossover design with participants allocated to 2 isocaloric arms: 1) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat achieved through a nutritional supplement; 2) CON: 55% carbohydrate, 15% protein, and 30% fat. Participants received the prescribed diets for 32 h while inside a whole-body calorimetry unit (WBCU). The first dietary intervention randomly offered in the WBCU was designed to maintain energy balance and the second matched what was offered during the first stay. Energy expenditure, macronutrient oxidation rates and balances, and metabolic blood markers were assessed. Body composition was measured at baseline using DXA.
Results
Forty-three healthy, normal-weight adults (19 females and 24 males) were included. Compared with the CON diet, the HP-TDR produced higher total energy expenditure (EE) 81 ± 82 kcal/d, P
Extra protein could give people a "metabolic advantage."
Inverse | Nov 27, 2020
...In the experiment, healthy people who ate high protein total diet replacement products burned more calories and fat over 32 hours, compared to people on a North American diet — a mix of various carbs, proteins, and fats. The protein group also ended the experiment burning more fat than they consumed, likely implying future weight loss over time.
The experiment also offers direct evidence that all calories aren't created equal.
"Our study proved that the same number of calories but from different diets can elicit different responses in energy metabolism," study co-authors Carla Prado and Camila Pinto (University of Alberta)....
While the study is limited to healthy people with a normal weight, scientists hope the findings will eventually lead to new interventions for people trying to manage a healthy weight — a step toward a longer life, free of disease.
...The team recruited a group of healthy, normal-weight adults between the ages of 18 and 35. Normal weight is defined as having a Body Mass Index between 18.5 and 24.9 kg/m.
Participants were then randomly split into one of two groups: one group was fed the high-protein total diet replacement, which consisted of 35 percent carbohydrate, 40 percent protein, and 25 percent fat. The product is a commercially available supplement comprised of soy protein, yogurt, and honey. (margd: I think original version of South Beach Diet aimed to keep carbs to 30% in 1st phase?)
The second group, or control group, was fed a diet with the same number of calories, but consisting of 55 percent carbohydrate, 15 percent protein, and 30 percent fat — what's considered a typical North American diet. Both groups received the prescribed diets for a 32-hour period while inside a metabolic chamber.
...On average, the high-protein total diet replacement, when compared to the North American diet, resulted in:
Higher energy expenditure
Increased fat oxidation
Negative fat balance, which implies body fat loss
"These results suggest that normal-weight individuals can have some metabolic advantages when consuming this type of nutritional product," the researchers explain.
It also suggests a higher proportion of protein might be beneficial compared to a diet consisting of the same number of calories, but with a lower proportion of protein...
https://www.inverse.com/mind-body/protein-weight-loss-study-explained
__________________________________________________________
Camila L P Oliveira et al. 2020. A high-protein total diet replacement increases energy expenditure and leads to negative fat balance in healthy, normal-weight adults. The American Journal of Clinical Nutrition (18 November 2020), https://doi.org/10.1093/ajcn/nqaa283 https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqaa283/5986961
ABSTRACT
Background
High-protein diets and total diet replacements are becoming increasingly popular for weight loss; however, further research is needed to elucidate their impact on the mechanisms involved in weight regulation.
Objective
The aim of this inpatient metabolic balance study was to compare the impact of a high-protein total diet replacement (HP-TDR) versus a control diet (CON) on select components of energy metabolism in healthy adults of both sexes.
Methods
The acute intervention was a randomized, controlled, crossover design with participants allocated to 2 isocaloric arms: 1) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat achieved through a nutritional supplement; 2) CON: 55% carbohydrate, 15% protein, and 30% fat. Participants received the prescribed diets for 32 h while inside a whole-body calorimetry unit (WBCU). The first dietary intervention randomly offered in the WBCU was designed to maintain energy balance and the second matched what was offered during the first stay. Energy expenditure, macronutrient oxidation rates and balances, and metabolic blood markers were assessed. Body composition was measured at baseline using DXA.
Results
Forty-three healthy, normal-weight adults (19 females and 24 males) were included. Compared with the CON diet, the HP-TDR produced higher total energy expenditure (EE) 81 ± 82 kcal/d, P
80margd
Fungal microbiome: Whether mice get fatter or thinner depends on the fungi that live in their gut
Kent Willis & Justin Stewart | March 5, 2021
...We found that mice whose gut microbiomes contained more of the fungi Thermomyces – which manufacturers use to break down fat in commercial processes – and less Saccharomyces – yeasts used in baking and brewing – gained about 15% more weight than the mice with different microbiomes. We found similar but smaller differences in mice on a normal diet.
Why it matters
The gut microbiome can influence metabolism.
Most people assume the microbiome is entirely bacteria. However, fungi – though usually less common than bacteria – are often critical members of these microbial communities. Microbiomes vary among individuals, so the species of fungi living in your gut might be different from your neighbor’s. This was also true for mice in our study.
Researchers only recently discovered the fungal microbiome and have limited knowledge of how it affects human health. Our study is one of the first to identify how gut fungi can influence metabolism.
If gut fungi influence metabolism in people similarly to the way they do in mice, researchers might be able to develop diets tailored for specific microbiomes. It might also be possible to adjust a person’s fungal microbiome to control weight in specific situations – such as after weight-loss surgery.
Scientists are still learning which species of fungi make their home in the gut versus fungi that might just be passing through. While many of the interactions between humans and their gut fungi are likely beneficial, this may not always be the case. For example, fungi may play a role in irritable bowel syndrome and increase the risk of developing pancreatic cancer.
Not only could the presence or absence of certain fungi have direct effects on health, fungal interaction with bacteria is also likely very important. Our work has made some key first steps in understanding the complex relationship between bacterial and fungal communities when they cooperate to digest processed food...
https://theconversation.com/fungal-microbiome-whether-mice-get-fatter-or-thinner...
---------------------------------------------------------
Tahliyah S. Mims et al. 2021. The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet. Communications Biology volume 4, Article number: 281 (5 March 2021) https://www.nature.com/articles/s42003-021-01820-z
Abstract
As an active interface between the host and their diet, the gut microbiota influences host metabolic adaptation; however, the contributions of fungi have been overlooked. Here, we investigate whether variations in gut mycobiome abundance and composition correlate with key features of host metabolism. We obtained animals from four commercial sources in parallel to test if differing starting mycobiomes can shape host adaptation in response to processed diets. We show that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic outcomes. We demonstrate that exposure to processed diet leads to persistent differences in fungal communities that significantly associate with differential deposition of body mass in male mice compared to mice fed standardized diet. Fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels are linked with alterations in fungal community diversity and composition. Specifically, variation in fungi from the genera Thermomyces and Saccharomyces most strongly associate with metabolic disturbance and weight gain. These data suggest that host–microbe metabolic interactions may be influenced by variability in the mycobiome. This work highlights the potential significance of the gut mycobiome in health and has implications for human and experimental metabolic studies.
...
RESULTS
Interkingdom composition of murine diets...
Gut fungal communities cluster by vendor...
Gut fungal community diversity declines with age and exposure to standard diet...
Gut fungal community composition changes on exposure to processed diet...
Gut fungal community composition differs between standard and processed diet...
Gut fungal community composition differs between standard and processed diet...
Exposure to processed diet reduces fungi-associated co-occurrence networks...
Metabolic tone is strongly associated with variability in the gut mycobiome...
Discussion
...we asked if differing starting mycobiomes could affect host adaptation to a standardized diet and an ultra-processed diet rich in purified carbohydrates in a manner that associated with deleterious metabolic outcomes. Our key findings are that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic changes in the host. For instance, increased triglyceride concentrations and metabolic biomarkers, including the deposition of hepatic lipids, correlate with increased abundance of the fungal genera Thermomyces and decreased Saccharomyces. Our results highlight the potential importance of the gut mycobiome in health and have implications for human and experimental metabolic studies.
The bacterial microbiome is strongly influenced by dietary exposure and influences host metabolism...However, despite evidence for fungal pattern recognition receptors in the human gut7 and fungal influences on the disease in the human gut, continuous gut colonization by fungi remains controversial in humans...In our (mouse) study, both prolonged exposure to a processed diet and length of isolation in a specific pathogen-free environment reduced fungal diversity. In turn, reduced fungal diversity was associated with increased adiposity and physiologic alterations seen in the metabolic syndrome.
...For metabolic studies in mice, the choice of vendor, shipment, diet, and housing may have instrumental roles in shaping outcomes, which should encourage further caution in drawing causative relationships...The implication for human microbiome studies, which often examine only bacteria and sample only fecal communities, is that the mycobiome may have unappreciated effects on microbiome-associated outcomes.
Exposure to a high-fat diet may alter fungal and interkingdom community composition...
Among the myriad metabolites and effectors that likely connect gut microbial communities to metabolism, the gut bacteriome may influence host metabolism through several major mechanisms...
Another important function of gut microbes, often attributed solely to bacteria, is the production of secondary bile acids (BAs). ...
In summary, these data indicate the gut mycobiome in healthy mice is highly variable and responds to disturbances such as changes in the environment and diet. Despite these ecological pressures, resilient differences in gut mycobiome composition in healthy mice strongly associated with differences in host metabolic tone, including differential fat deposition, metabolic biomarkers, and gene expression in metabolic tissues. We also highlighted two fungal-derived products with plausible effects on host metabolism. While there are potentially thousands of metabolically active fungal products, our work argues for future work in defined gnotobiotic animal models to further elucidate the mechanisms of mycobiome-host interaction. Finally, our findings suggest that differences in the gut mycobiome may be an underappreciated source of variability in health and metabolic outcomes in response to dietary interventions.
Kent Willis & Justin Stewart | March 5, 2021
...We found that mice whose gut microbiomes contained more of the fungi Thermomyces – which manufacturers use to break down fat in commercial processes – and less Saccharomyces – yeasts used in baking and brewing – gained about 15% more weight than the mice with different microbiomes. We found similar but smaller differences in mice on a normal diet.
Why it matters
The gut microbiome can influence metabolism.
Most people assume the microbiome is entirely bacteria. However, fungi – though usually less common than bacteria – are often critical members of these microbial communities. Microbiomes vary among individuals, so the species of fungi living in your gut might be different from your neighbor’s. This was also true for mice in our study.
Researchers only recently discovered the fungal microbiome and have limited knowledge of how it affects human health. Our study is one of the first to identify how gut fungi can influence metabolism.
If gut fungi influence metabolism in people similarly to the way they do in mice, researchers might be able to develop diets tailored for specific microbiomes. It might also be possible to adjust a person’s fungal microbiome to control weight in specific situations – such as after weight-loss surgery.
Scientists are still learning which species of fungi make their home in the gut versus fungi that might just be passing through. While many of the interactions between humans and their gut fungi are likely beneficial, this may not always be the case. For example, fungi may play a role in irritable bowel syndrome and increase the risk of developing pancreatic cancer.
Not only could the presence or absence of certain fungi have direct effects on health, fungal interaction with bacteria is also likely very important. Our work has made some key first steps in understanding the complex relationship between bacterial and fungal communities when they cooperate to digest processed food...
https://theconversation.com/fungal-microbiome-whether-mice-get-fatter-or-thinner...
---------------------------------------------------------
Tahliyah S. Mims et al. 2021. The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet. Communications Biology volume 4, Article number: 281 (5 March 2021) https://www.nature.com/articles/s42003-021-01820-z
Abstract
As an active interface between the host and their diet, the gut microbiota influences host metabolic adaptation; however, the contributions of fungi have been overlooked. Here, we investigate whether variations in gut mycobiome abundance and composition correlate with key features of host metabolism. We obtained animals from four commercial sources in parallel to test if differing starting mycobiomes can shape host adaptation in response to processed diets. We show that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic outcomes. We demonstrate that exposure to processed diet leads to persistent differences in fungal communities that significantly associate with differential deposition of body mass in male mice compared to mice fed standardized diet. Fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels are linked with alterations in fungal community diversity and composition. Specifically, variation in fungi from the genera Thermomyces and Saccharomyces most strongly associate with metabolic disturbance and weight gain. These data suggest that host–microbe metabolic interactions may be influenced by variability in the mycobiome. This work highlights the potential significance of the gut mycobiome in health and has implications for human and experimental metabolic studies.
...
RESULTS
Interkingdom composition of murine diets...
Gut fungal communities cluster by vendor...
Gut fungal community diversity declines with age and exposure to standard diet...
Gut fungal community composition changes on exposure to processed diet...
Gut fungal community composition differs between standard and processed diet...
Gut fungal community composition differs between standard and processed diet...
Exposure to processed diet reduces fungi-associated co-occurrence networks...
Metabolic tone is strongly associated with variability in the gut mycobiome...
Discussion
...we asked if differing starting mycobiomes could affect host adaptation to a standardized diet and an ultra-processed diet rich in purified carbohydrates in a manner that associated with deleterious metabolic outcomes. Our key findings are that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic changes in the host. For instance, increased triglyceride concentrations and metabolic biomarkers, including the deposition of hepatic lipids, correlate with increased abundance of the fungal genera Thermomyces and decreased Saccharomyces. Our results highlight the potential importance of the gut mycobiome in health and have implications for human and experimental metabolic studies.
The bacterial microbiome is strongly influenced by dietary exposure and influences host metabolism...However, despite evidence for fungal pattern recognition receptors in the human gut7 and fungal influences on the disease in the human gut, continuous gut colonization by fungi remains controversial in humans...In our (mouse) study, both prolonged exposure to a processed diet and length of isolation in a specific pathogen-free environment reduced fungal diversity. In turn, reduced fungal diversity was associated with increased adiposity and physiologic alterations seen in the metabolic syndrome.
...For metabolic studies in mice, the choice of vendor, shipment, diet, and housing may have instrumental roles in shaping outcomes, which should encourage further caution in drawing causative relationships...The implication for human microbiome studies, which often examine only bacteria and sample only fecal communities, is that the mycobiome may have unappreciated effects on microbiome-associated outcomes.
Exposure to a high-fat diet may alter fungal and interkingdom community composition...
Among the myriad metabolites and effectors that likely connect gut microbial communities to metabolism, the gut bacteriome may influence host metabolism through several major mechanisms...
Another important function of gut microbes, often attributed solely to bacteria, is the production of secondary bile acids (BAs). ...
In summary, these data indicate the gut mycobiome in healthy mice is highly variable and responds to disturbances such as changes in the environment and diet. Despite these ecological pressures, resilient differences in gut mycobiome composition in healthy mice strongly associated with differences in host metabolic tone, including differential fat deposition, metabolic biomarkers, and gene expression in metabolic tissues. We also highlighted two fungal-derived products with plausible effects on host metabolism. While there are potentially thousands of metabolically active fungal products, our work argues for future work in defined gnotobiotic animal models to further elucidate the mechanisms of mycobiome-host interaction. Finally, our findings suggest that differences in the gut mycobiome may be an underappreciated source of variability in health and metabolic outcomes in response to dietary interventions.
81margd
Hungry?
"For the 1st time in a large-scale controlled study of healthy individuals representative of the general population, our data show that postprandial glucose dips are common & lead to increased hunger and energy consumption in real-world conditions"
Image ( https://twitter.com/EricTopol/status/1381639868200054790/photo/1 )
Nature Metabolism https://nature.com/articles/s42255-021-00383-x *
- Eric Topol (physician scientist Scripps) @EricTopol | 12:06 PM · Apr 12, 2021
------------------------------------------------------------------------------
* Patrick Wyatt et al. 2021. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals. Nature Metabolism (12 April 2021) https://nature.com/articles/s42255-021-00383-x
Abstract
Understanding how to modulate appetite in humans is key to developing successful weight loss interventions. Here, we showed that postprandial glucose dips 2–3 h after a meal are a better predictor of postprandial self-reported hunger and subsequent energy intake than peak glucose at 0–2 h and glucose incremental area under the blood glucose curve at 0–2 h. We explore the links among postprandial glucose, appetite and subsequent energy intake in 1,070 participants from a UK exploratory and US validation cohort, who consumed 8,624 standardized meals followed by 71,715 ad libitum meals, using continuous glucose monitors to record postprandial glycaemia. For participants eating each of the standardized meals, the average postprandial glucose dip at 2–3 h relative to baseline level predicted an increase in hunger at 2–3 h (r = 0.16...), shorter time until next meal (r = −0.14...), greater energy intake at 3–4 h (r = 0.19...) and greater energy intake at 24 h (r = 0.27...). Results were directionally consistent in the US validation cohort. These data provide a quantitative assessment of the relevance of postprandial glycaemia in appetite and energy intake modulation.
"For the 1st time in a large-scale controlled study of healthy individuals representative of the general population, our data show that postprandial glucose dips are common & lead to increased hunger and energy consumption in real-world conditions"
Image ( https://twitter.com/EricTopol/status/1381639868200054790/photo/1 )
Nature Metabolism https://nature.com/articles/s42255-021-00383-x *
- Eric Topol (physician scientist Scripps) @EricTopol | 12:06 PM · Apr 12, 2021
------------------------------------------------------------------------------
* Patrick Wyatt et al. 2021. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals. Nature Metabolism (12 April 2021) https://nature.com/articles/s42255-021-00383-x
Abstract
Understanding how to modulate appetite in humans is key to developing successful weight loss interventions. Here, we showed that postprandial glucose dips 2–3 h after a meal are a better predictor of postprandial self-reported hunger and subsequent energy intake than peak glucose at 0–2 h and glucose incremental area under the blood glucose curve at 0–2 h. We explore the links among postprandial glucose, appetite and subsequent energy intake in 1,070 participants from a UK exploratory and US validation cohort, who consumed 8,624 standardized meals followed by 71,715 ad libitum meals, using continuous glucose monitors to record postprandial glycaemia. For participants eating each of the standardized meals, the average postprandial glucose dip at 2–3 h relative to baseline level predicted an increase in hunger at 2–3 h (r = 0.16...), shorter time until next meal (r = −0.14...), greater energy intake at 3–4 h (r = 0.19...) and greater energy intake at 24 h (r = 0.27...). Results were directionally consistent in the US validation cohort. These data provide a quantitative assessment of the relevance of postprandial glycaemia in appetite and energy intake modulation.
82margd
Perspective / Hypothesis:
John R. Speakman and Kevin D. Hall. 2021. Carbohydrates, insulin, and obesity. Science 07 May 2021: Vol. 372, Issue 6542, pp. 577-578 . DOI: 10.1126/science.aav0448 https://science.sciencemag.org/content/372/6542/577
John R. Speakman and Kevin D. Hall. 2021. Carbohydrates, insulin, and obesity. Science 07 May 2021: Vol. 372, Issue 6542, pp. 577-578 . DOI: 10.1126/science.aav0448 https://science.sciencemag.org/content/372/6542/577
83margd
Leptin is important for brain development (hippocampus).
Semra Sahin et al. 2021. Leptin increases GABAergic synaptogenesis through the Rho guanine exchange factor β-PIX in developing hippocampal neurons (Research Article). Science Signaling 18 May 2021: Vol. 14, Issue 683, eabe4111 DOI:10.1126/scisignal.abe4111 https://stke.sciencemag.org/content/14/683/eabe4111
Early-life malnutrition is associated with neurodevelopmental disorders. Sahin et al. found that leptin—a hormone produced by fat cells that induces the feeling of satiety—is critical for the development of inhibitory GABAergic synapses in the brain. In cultured hippocampal neurons from male and female rat pups, leptin enhanced the formation of a series of physical and functional protein interactions involving the leptin receptor, the guanine exchange factor (GEF) β-PIX, the kinase CaMK, and GABAA receptors that together resulted in increased abundance of GABAA receptors at the synapse. The findings reveal how leptin facilitates neuronal connectivity in the developing hippocampus and may provide clues in understanding and treating neurodevelopmental disorders.
Semra Sahin et al. 2021. Leptin increases GABAergic synaptogenesis through the Rho guanine exchange factor β-PIX in developing hippocampal neurons (Research Article). Science Signaling 18 May 2021: Vol. 14, Issue 683, eabe4111 DOI:10.1126/scisignal.abe4111 https://stke.sciencemag.org/content/14/683/eabe4111
Early-life malnutrition is associated with neurodevelopmental disorders. Sahin et al. found that leptin—a hormone produced by fat cells that induces the feeling of satiety—is critical for the development of inhibitory GABAergic synapses in the brain. In cultured hippocampal neurons from male and female rat pups, leptin enhanced the formation of a series of physical and functional protein interactions involving the leptin receptor, the guanine exchange factor (GEF) β-PIX, the kinase CaMK, and GABAA receptors that together resulted in increased abundance of GABAA receptors at the synapse. The findings reveal how leptin facilitates neuronal connectivity in the developing hippocampus and may provide clues in understanding and treating neurodevelopmental disorders.
84margd
Paleo carbs?
How ancient people fell in love with bread, beer and other carbs
Well before people domesticated crops, they were grinding grains for hearty stews and other starchy dishes.
Andrew Curry 22 June 2021
...The sheer number of grain-processing tools at Göbekli Tepe (in ) suggest that (12,000 years ago) even before farming took hold, cereals were a daily staple, not just part of an occasional fermented treat.
Nature 594, 488-491 (2021)
doi: https://doi.org/10.1038/d41586-021-01681-whttps://www.nature.com/articles/d41586...
How ancient people fell in love with bread, beer and other carbs
Well before people domesticated crops, they were grinding grains for hearty stews and other starchy dishes.
Andrew Curry 22 June 2021
...The sheer number of grain-processing tools at Göbekli Tepe (in ) suggest that (12,000 years ago) even before farming took hold, cereals were a daily staple, not just part of an occasional fermented treat.
Nature 594, 488-491 (2021)
doi: https://doi.org/10.1038/d41586-021-01681-whttps://www.nature.com/articles/d41586...
85margd
In mice at least, inhibition of gene variant GPR75 may be a therapeutic strategy for obesity.
Giles S. H. Yeo, Stephen O'Rahilly. 2021. Finding genes that control body weight (Perspective). Science 02 Jul 2021: Vol. 373, Issue 6550, pp. 30-31. DOI: 10.1126/science.abh3556 https://science.sciencemag.org/content/373/6550/30
Summary
Obesity is a common disorder with major adverse effects on morbidity and mortality. Genetic factors play an important role in determining the extent to which people acquire energy and store it as fat, which has implications for the risk of developing obesity. Studies in patients with severe early-onset obesity have identified mutations in >20 pmackey: genes that have a large effect on body mass index (BMI) (1), whereas genome-wide association studies (GWASs) in large populations have identified hundreds of common variants with more-subtle effects (2). On page 73 of this issue, Akbari et al. (3) report rare genetic variants influencing BMI identified through whole-exome sequencing of >600,000 people from the United Kingdom, the United States, and Mexico. The authors identified genes in which rare nonsynonymous variants were associated with either higher or lower BMI, bringing insight to the genetics underlying human adiposity.
---------------------------------------------------------------
Parsa Akbari et al. 2021. Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity (Research Article). Science 02 Jul 2021: Vol. 373, Issue 6550, eabf8683
DOI: 10.1126/science.abf8683 https://science.sciencemag.org/content/373/6550/eabf8683
How genes affect human obesity
Obesity is linked to many human diseases, including diabetes, cancer, and heart disease. There is thus great interest in understanding how genes predispose individuals to, or protect individuals from, obesity. Akbari et al. sequenced more than 600,000 exomes from the United Kingdom, the United States, and Mexico and identified 16 rare coding variants (see the Perspective by Yeo and O'Rahilly (above)). Some of the alleles associated with body mass index (BMI) were brain-expressed G protein–coupled receptors. One variant allele was found in Mexican populations at low frequency and was associated with lower BMI. Deletion of this gene in mice resulted in a resistance to weight gain, suggesting that this gene provides an avenue of study for the prevention or treatment of obesity.
Structured Abstract
INTRODUCTION...
RATIONALE
...We sequenced the exomes of 645,626 individuals from the UK, the US, and Mexico and estimated associations of rare coding variants with body mass index (BMI), a measure of overall adiposity used to define obesity in clinical practice. We complemented exome sequencing with fine-mapping of common alleles, polygenic score analysis, and in vitro and in vivo modeling work.
RESULTS
We identified 16 genes for which the burden of rare nonsynonymous variants was associated with BMI at exome-wide statistical significance ..., including associations at five brain-expressed G protein–coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). We observed an overrepresentation of genes highly expressed in the hypothalamus, a key center for the neuroendocrine regulation of energy balance. Protein-truncating variants in GPR75 were found in ~4/10,000 sequenced people and were associated with 1.8 kg/m2 lower BMI, 5.3 kg lower bodyweight, and 54% lower odds of obesity in heterozygous carriers. Knock out of Gpr75 in mice resulted in resistance to weight gain in a high-fat diet model, which was allele-dose dependent (25% and 44% lower weight gain, respectively, for heterozygous Gpr75−/+ mice and knockout Gpr75−/− mice compared with wild type) and accompanied by improved glycemic control and insulin sensitivity. Protein-truncating variants in CALCR were associated with higher BMI and obesity risk, whereas protein-truncating variants in GIPR and two missense alleles Arg190→Gln (Arg190Gln), Glu288Gly, which we show result in loss of function in vitro, were associated with lower adiposity. Among monogenic obesity genes in the leptin-melanocortin pathway, heterozygous predicted loss-of-function variants in LEP, POMC, PCSK1, and MC4R (but not LEPR) were associated with higher BMI. Rare protein-truncating variants in UBR2, ANO4, and PCSK1 were associated with more than twofold higher odds of obesity in heterozygous carriers, similar to predicted-deleterious nonsynonymous variants in MC4R, which are considered the most common cause of monogenic obesity. Polygenic predisposition due to more than 2 million common genetic variants influenced the penetrance of obesity in rare variant carriers in an additive fashion.
CONCLUSION
These results suggest that inhibition of GPR75 may be a therapeutic strategy for obesity and illustrate the power of massive-scale exome sequencing for the identification of large-effect coding variant associations and drug targets for complex traits.
Giles S. H. Yeo, Stephen O'Rahilly. 2021. Finding genes that control body weight (Perspective). Science 02 Jul 2021: Vol. 373, Issue 6550, pp. 30-31. DOI: 10.1126/science.abh3556 https://science.sciencemag.org/content/373/6550/30
Summary
Obesity is a common disorder with major adverse effects on morbidity and mortality. Genetic factors play an important role in determining the extent to which people acquire energy and store it as fat, which has implications for the risk of developing obesity. Studies in patients with severe early-onset obesity have identified mutations in >20 pmackey: genes that have a large effect on body mass index (BMI) (1), whereas genome-wide association studies (GWASs) in large populations have identified hundreds of common variants with more-subtle effects (2). On page 73 of this issue, Akbari et al. (3) report rare genetic variants influencing BMI identified through whole-exome sequencing of >600,000 people from the United Kingdom, the United States, and Mexico. The authors identified genes in which rare nonsynonymous variants were associated with either higher or lower BMI, bringing insight to the genetics underlying human adiposity.
---------------------------------------------------------------
Parsa Akbari et al. 2021. Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity (Research Article). Science 02 Jul 2021: Vol. 373, Issue 6550, eabf8683
DOI: 10.1126/science.abf8683 https://science.sciencemag.org/content/373/6550/eabf8683
How genes affect human obesity
Obesity is linked to many human diseases, including diabetes, cancer, and heart disease. There is thus great interest in understanding how genes predispose individuals to, or protect individuals from, obesity. Akbari et al. sequenced more than 600,000 exomes from the United Kingdom, the United States, and Mexico and identified 16 rare coding variants (see the Perspective by Yeo and O'Rahilly (above)). Some of the alleles associated with body mass index (BMI) were brain-expressed G protein–coupled receptors. One variant allele was found in Mexican populations at low frequency and was associated with lower BMI. Deletion of this gene in mice resulted in a resistance to weight gain, suggesting that this gene provides an avenue of study for the prevention or treatment of obesity.
Structured Abstract
INTRODUCTION...
RATIONALE
...We sequenced the exomes of 645,626 individuals from the UK, the US, and Mexico and estimated associations of rare coding variants with body mass index (BMI), a measure of overall adiposity used to define obesity in clinical practice. We complemented exome sequencing with fine-mapping of common alleles, polygenic score analysis, and in vitro and in vivo modeling work.
RESULTS
We identified 16 genes for which the burden of rare nonsynonymous variants was associated with BMI at exome-wide statistical significance ..., including associations at five brain-expressed G protein–coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). We observed an overrepresentation of genes highly expressed in the hypothalamus, a key center for the neuroendocrine regulation of energy balance. Protein-truncating variants in GPR75 were found in ~4/10,000 sequenced people and were associated with 1.8 kg/m2 lower BMI, 5.3 kg lower bodyweight, and 54% lower odds of obesity in heterozygous carriers. Knock out of Gpr75 in mice resulted in resistance to weight gain in a high-fat diet model, which was allele-dose dependent (25% and 44% lower weight gain, respectively, for heterozygous Gpr75−/+ mice and knockout Gpr75−/− mice compared with wild type) and accompanied by improved glycemic control and insulin sensitivity. Protein-truncating variants in CALCR were associated with higher BMI and obesity risk, whereas protein-truncating variants in GIPR and two missense alleles Arg190→Gln (Arg190Gln), Glu288Gly, which we show result in loss of function in vitro, were associated with lower adiposity. Among monogenic obesity genes in the leptin-melanocortin pathway, heterozygous predicted loss-of-function variants in LEP, POMC, PCSK1, and MC4R (but not LEPR) were associated with higher BMI. Rare protein-truncating variants in UBR2, ANO4, and PCSK1 were associated with more than twofold higher odds of obesity in heterozygous carriers, similar to predicted-deleterious nonsynonymous variants in MC4R, which are considered the most common cause of monogenic obesity. Polygenic predisposition due to more than 2 million common genetic variants influenced the penetrance of obesity in rare variant carriers in an additive fashion.
CONCLUSION
These results suggest that inhibition of GPR75 may be a therapeutic strategy for obesity and illustrate the power of massive-scale exome sequencing for the identification of large-effect coding variant associations and drug targets for complex traits.
86margd
Breaking Down the ‘Wellness-Industrial Complex,’ an Episode at a Time
Victoria Petersen | Sept. 9, 2021
The “Maintenance Phase” podcast interrogates the science behind health food trends, fad diets and popular nutritional advice.
https://www.nytimes.com/2021/09/09/dining/wellness-industrial-complex-maintenanc...
Victoria Petersen | Sept. 9, 2021
The “Maintenance Phase” podcast interrogates the science behind health food trends, fad diets and popular nutritional advice.
https://www.nytimes.com/2021/09/09/dining/wellness-industrial-complex-maintenanc...
87margd
How a ‘fatally, tragically flawed’ paradigm has derailed the science of obesity
Gary Taubes Sept. 13, 2021
...16 influential academic researchers...lengthy review the American Journal of Clinical Nutrition ...The principal author is David Ludwig, a professor of pediatrics at Harvard Medical School and of nutrition at the Harvard T.H. Chan School of Public Health. We argue that the reason so little progress has been made against obesity and type 2 diabetes is because the field has been laboring, quite literally, in the sense intended by philosopher of science Thomas Kuhn, under the wrong paradigm.
This energy-in-energy-out conception of weight regulation, we argue, is fatally, tragically flawed: Obesity is not an energy balance disorder, but a hormonal or constitutional disorder, a dysregulation of fat storage and metabolism, a disorder of fuel-partitioning. Because these hormonal responses are dominated by the insulin signaling system, which in turn responds primarily (although not entirely) to the carbohydrate content of the diet, this thinking is now known as the carbohydrate-insulin model.
Its implications are simple and profound: People don’t get fat because they eat too much, consuming more calories than they expend, but because the carbohydrates in their diets — both the quantity of carbohydrates and their quality — establish a hormonal milieu that fosters the accumulation of excess fat...
https://www.statnews.com/2021/09/13/how-a-fatally-tragically-flawed-paradigm-has...
------------------------------------------------------------
David S Ludwig et al. 2021. The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. The American Journal of Clinical Nutrition, nqab270, Published:
13 September 2021. https://doi.org/10.1093/ajcn/nqab270 https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab270/6369073
ABSTRACT
According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.
...
Conclusions
As with virtually all models of complex biological phenomena, the iteration of the CIM presented here cannot provide a complete and precise representation of all causal mechanisms; nor does it preclude the existence of other causative influences. The value of a scientific model is in stimulating discourse and informing the design of research. Premature claims to have falsified or refuted the CIM, based on weak and confounded evidence, impede constructive scientific discourse. Controversy notwithstanding, important common ground may already exist. For instance, hardwired hedonic preferences for sweetness may drive consumption of sugary foods (consistent with the EBM), which in turn may also affect substrate partitioning through calorie-independent mechanisms (consistent with the CIM). In this sense, conventional notions of palatability and the metabolic effects of preferred foods would work in concert to drive fat accumulation. Or perhaps time-restricted eating could reduce hunger and thereby facilitate calorie restriction, in part through hormonal mechanisms...
The field of obesity should embrace paradigm clash as an essential step forward. Toward this end, investigators should, first, refrain from hyperbolic claims to have disproven (or proven) alternative explanations of the obesity pandemic; second, clarify the EBM, specifying contrasting causal and testable hypotheses; third, form collaborations among scientists with diverse viewpoints to test predictions in rigorous and unbiased research; and fourth, to facilitate these aims, depersonalize the debate, scrupulously avoiding ad hominem argument. Rigorous research using complementary designs will be needed to resolve the debate, clarify a middle ground, or point the way to new explanatory models that better encompass the evidence. With the massive and growing burden of obesity-related diseases throughout the world, this work must assume priority.
Gary Taubes Sept. 13, 2021
...16 influential academic researchers...lengthy review the American Journal of Clinical Nutrition ...The principal author is David Ludwig, a professor of pediatrics at Harvard Medical School and of nutrition at the Harvard T.H. Chan School of Public Health. We argue that the reason so little progress has been made against obesity and type 2 diabetes is because the field has been laboring, quite literally, in the sense intended by philosopher of science Thomas Kuhn, under the wrong paradigm.
This energy-in-energy-out conception of weight regulation, we argue, is fatally, tragically flawed: Obesity is not an energy balance disorder, but a hormonal or constitutional disorder, a dysregulation of fat storage and metabolism, a disorder of fuel-partitioning. Because these hormonal responses are dominated by the insulin signaling system, which in turn responds primarily (although not entirely) to the carbohydrate content of the diet, this thinking is now known as the carbohydrate-insulin model.
Its implications are simple and profound: People don’t get fat because they eat too much, consuming more calories than they expend, but because the carbohydrates in their diets — both the quantity of carbohydrates and their quality — establish a hormonal milieu that fosters the accumulation of excess fat...
https://www.statnews.com/2021/09/13/how-a-fatally-tragically-flawed-paradigm-has...
------------------------------------------------------------
David S Ludwig et al. 2021. The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. The American Journal of Clinical Nutrition, nqab270, Published:
13 September 2021. https://doi.org/10.1093/ajcn/nqab270 https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab270/6369073
ABSTRACT
According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.
...
Conclusions
As with virtually all models of complex biological phenomena, the iteration of the CIM presented here cannot provide a complete and precise representation of all causal mechanisms; nor does it preclude the existence of other causative influences. The value of a scientific model is in stimulating discourse and informing the design of research. Premature claims to have falsified or refuted the CIM, based on weak and confounded evidence, impede constructive scientific discourse. Controversy notwithstanding, important common ground may already exist. For instance, hardwired hedonic preferences for sweetness may drive consumption of sugary foods (consistent with the EBM), which in turn may also affect substrate partitioning through calorie-independent mechanisms (consistent with the CIM). In this sense, conventional notions of palatability and the metabolic effects of preferred foods would work in concert to drive fat accumulation. Or perhaps time-restricted eating could reduce hunger and thereby facilitate calorie restriction, in part through hormonal mechanisms...
The field of obesity should embrace paradigm clash as an essential step forward. Toward this end, investigators should, first, refrain from hyperbolic claims to have disproven (or proven) alternative explanations of the obesity pandemic; second, clarify the EBM, specifying contrasting causal and testable hypotheses; third, form collaborations among scientists with diverse viewpoints to test predictions in rigorous and unbiased research; and fourth, to facilitate these aims, depersonalize the debate, scrupulously avoiding ad hominem argument. Rigorous research using complementary designs will be needed to resolve the debate, clarify a middle ground, or point the way to new explanatory models that better encompass the evidence. With the massive and growing burden of obesity-related diseases throughout the world, this work must assume priority.
882wonderY
>87 margd: The film documentary Fed Up covers some of those issues for the layperson, if imperfectly. It was enlightening to me, as I’d been taught that all calories were equal. I’ve also read a couple of books concerned with gut biome variations and nutrition.
89margd
An example of how our ancestors' experiences with famine and plenty shaped our genotypes: the 15% of E Asians with this gene variant could be weight-challenged in a time of plenty?
In a gene tied to growth, scientists see glimmers of human history
University at Buffalo | September 24, 2021
...The research shows, through multiple avenues, that a shortened version of the gene—a variant known as GHRd3—may help people survive in situations where resources are scarce or unpredictable...
Here's the story the study tells: GHRd3 emerged about 1-2 million years ago, and was likely the overwhelmingly predominant version of the gene in the ancestors of modern humans, as well as in Neanderthals and Denisovans.
Then, "In the last 50,000 years or so, this variant becomes less prevalent, and you have a massive decrease in the frequency of this variant among East Asian populations we studied, where we see the estimated allele frequency drop from 85% to 15% during the last 30,000 years," says University at Buffalo evolutionary biologist Omer Gokcumen. "So the question becomes: Why? Was this variant favored in the past, and it fell out of evolutionary favor recently? Or is what we are observing just a blip among the complexity of genomes?"
..."We think that this variant is beneficial where there are periods of starvation, which was the case for most of human evolution," says Gokcumen, Ph.D., associate professor of biological sciences in the UB College of Arts and Sciences. With regard to GHRd3's waning prominence in recent human history, he speculates that, "Maybe the rapid technological and cultural advances over the past 50,000 years have created a buffer against some of the fluctuations in resources that made GHRd3 so advantageous in the past."
...the GHRd3 variant was associated with better outcomes in a group of children who had endured and survived severe malnutrition.
...when scientists placed male mice with GHRd3 on a low-calorie diet, the animals were smaller at 2 months old than counterparts without the variant. This may be beneficial in times of nutritional stress, as smaller bodies need less food. Because the effects of GHRd3 were not as prominent in females, male and female mice carrying the variant ended up being the same size when they were on a low-calorie diet (usually, males are significantly larger than females)...
https://phys.org/news/2021-09-gene-tied-growth-scientists-glimmers.html
_____________________________________________
Marie Saitou et al. 2021. Sex-specific phenotypic effects and evolutionary history of an ancient polymorphic deletion of the human growth hormone receptor. Science Advances • 24 Sep 2021 • Vol 7, Issue 39 • DOI: 10.1126/sciadv.abi4476 https://www.science.org/doi/abs/10.1126/sciadv.abi4476 https://www.science.org/doi/abs/10.1126/sciadv.abi4476
Abstract
The common deletion of the third exon of the growth hormone receptor gene (GHRd3) in humans is associated with birth weight, growth after birth, and time of puberty. However, its evolutionary history and the molecular mechanisms through which it affects phenotypes remain unresolved. We present evidence that this deletion was nearly fixed in the ancestral population of anatomically modern humans and Neanderthals but underwent a recent adaptive reduction in frequency in East Asia. We documented that GHRd3 is associated with protection from severe malnutrition. Using a novel mouse model, we found that, under calorie restriction, Ghrd3 leads to the female-like gene expression in male livers and the disappearance of sexual dimorphism in weight. The sex- and diet-dependent effects of GHRd3 in our mouse model are consistent with a model in which the allele frequency of GHRd3 varies throughout human evolution as a response to fluctuations in resource availability.
In a gene tied to growth, scientists see glimmers of human history
University at Buffalo | September 24, 2021
...The research shows, through multiple avenues, that a shortened version of the gene—a variant known as GHRd3—may help people survive in situations where resources are scarce or unpredictable...
Here's the story the study tells: GHRd3 emerged about 1-2 million years ago, and was likely the overwhelmingly predominant version of the gene in the ancestors of modern humans, as well as in Neanderthals and Denisovans.
Then, "In the last 50,000 years or so, this variant becomes less prevalent, and you have a massive decrease in the frequency of this variant among East Asian populations we studied, where we see the estimated allele frequency drop from 85% to 15% during the last 30,000 years," says University at Buffalo evolutionary biologist Omer Gokcumen. "So the question becomes: Why? Was this variant favored in the past, and it fell out of evolutionary favor recently? Or is what we are observing just a blip among the complexity of genomes?"
..."We think that this variant is beneficial where there are periods of starvation, which was the case for most of human evolution," says Gokcumen, Ph.D., associate professor of biological sciences in the UB College of Arts and Sciences. With regard to GHRd3's waning prominence in recent human history, he speculates that, "Maybe the rapid technological and cultural advances over the past 50,000 years have created a buffer against some of the fluctuations in resources that made GHRd3 so advantageous in the past."
...the GHRd3 variant was associated with better outcomes in a group of children who had endured and survived severe malnutrition.
...when scientists placed male mice with GHRd3 on a low-calorie diet, the animals were smaller at 2 months old than counterparts without the variant. This may be beneficial in times of nutritional stress, as smaller bodies need less food. Because the effects of GHRd3 were not as prominent in females, male and female mice carrying the variant ended up being the same size when they were on a low-calorie diet (usually, males are significantly larger than females)...
https://phys.org/news/2021-09-gene-tied-growth-scientists-glimmers.html
_____________________________________________
Marie Saitou et al. 2021. Sex-specific phenotypic effects and evolutionary history of an ancient polymorphic deletion of the human growth hormone receptor. Science Advances • 24 Sep 2021 • Vol 7, Issue 39 • DOI: 10.1126/sciadv.abi4476 https://www.science.org/doi/abs/10.1126/sciadv.abi4476 https://www.science.org/doi/abs/10.1126/sciadv.abi4476
Abstract
The common deletion of the third exon of the growth hormone receptor gene (GHRd3) in humans is associated with birth weight, growth after birth, and time of puberty. However, its evolutionary history and the molecular mechanisms through which it affects phenotypes remain unresolved. We present evidence that this deletion was nearly fixed in the ancestral population of anatomically modern humans and Neanderthals but underwent a recent adaptive reduction in frequency in East Asia. We documented that GHRd3 is associated with protection from severe malnutrition. Using a novel mouse model, we found that, under calorie restriction, Ghrd3 leads to the female-like gene expression in male livers and the disappearance of sexual dimorphism in weight. The sex- and diet-dependent effects of GHRd3 in our mouse model are consistent with a model in which the allele frequency of GHRd3 varies throughout human evolution as a response to fluctuations in resource availability.
90margd
Why Exercise Is More Important Than Weight Loss for a Longer Life
People typically lower their risks of heart disease and premature death far more by gaining fitness than by dropping weight.
Gretchen Reynolds | Sept. 29, 2021
For better health and a longer life span, exercise is more important than weight loss, especially if you are overweight or obese, according to an interesting new review of the relationships between fitness, weight, heart health and longevity. The study, which analyzed the results of hundreds of previous studies of weight loss and workouts in men and women, found that obese people typically lower their risks of heart disease and premature death far more by gaining fitness than by dropping weight or dieting.
Glenn Gaesser, a professor of exercise physiology at Arizona State University in Phoenix,...and his colleague Siddhartha Angadi, a professor of education and kinesiology at the University of Virginia in Charlottesville, began scouring research databases for past studies related to dieting, exercise, fitness, metabolic health and longevity. They were especially interested in meta-analyses, which pool and analyze data from multiple past studies, allowing researchers to look at results from far more people than in most individual studies of weight loss or exercise, which tend to be small-scale.
...As a whole, the studies they cite show that sedentary, obese men and women who begin to exercise and improve their fitness can lower their risk of premature death by as much as 30 percent or more, even if their weight does not budge. This improvement generally puts them at lower risk of early death than people who are considered to be of normal weight but out of shape, Dr. Gaesser said.
On the other hand, if heavy people lose weight by dieting (not illness), their statistical risk of dying young typically drops by about 16 percent, but not in all studies. Some of the research cited in the new review finds that weight loss among obese people does not decrease mortality risks at all.
...people who shed pounds by dieting regained them, then tried again, a yo-yo approach to weight loss that often contributes to metabolic problems like diabetes and high cholesterol and lower life expectancy.
On the other hand, exercise combats those same conditions, (Gaesser) said. It may also, unexpectedly, remake people’s fat stores. “People with obesity usually lose some visceral fat when they exercise,” he said, even if their overall weight loss is negligible. Visceral fat, which collects deep inside our bodies, raises risks for Type 2 diabetes, heart disease and other conditions.
A few of the studies they cite find that exercise likewise alters molecular signaling inside other fat cells in ways that may improve insulin resistance, no matter how much weight someone carries. “It looks like exercise makes fat more fit,” Dr. Gaesser said.
The primary takeaway of the new review, he concluded, is that you do not need to lose weight to be healthy. “You will be better off, in terms of mortality risk, by increasing your physical activity and fitness than by intentionally losing weight,” he said.
https://www.nytimes.com/2021/09/29/well/move/exercise-weight-loss-longer-life.ht...
----------------------------------------------------------------------------
GA Gaesser & SS Angadi. 2021. Obesity treatment: Weight loss versus increasing fitness and physical activity for reducing health risks (Review). Cell. Published:September 20, 2021 DOI:https://doi.org/10.1016/j.isci.2021.102995 https://www.cell.com/iscience/fulltext/S2589-0042(21)00963-9
Summary
We propose a weight-neutral strategy for obesity treatment on the following grounds: (1) the mortality risk associated with obesity is largely attenuated or eliminated by moderate-to-high levels of cardiorespiratory fitness (CRF) or physical activity (PA), (2) most cardiometabolic risk markers associated with obesity can be improved with exercise training independent of weight loss and by a magnitude similar to that observed with weight-loss programs, (3) weight loss, even if intentional, is not consistently associated with lower mortality risk, (4) increases in CRF or PA are consistently associated with greater reductions in mortality risk than is intentional weight loss, and (5) weight cycling is associated with numerous adverse health outcomes including increased mortality. Adherence to PA may improve if health care professionals consider PA and CRF as essential vital signs and consistently emphasize to their patients the myriad benefits of PA and CRF in the absence of weight loss.
Introduction...
The BMI – mortality relationship: Influence of cardiorespiratory fitness and physical activity...
Cardiorespiratory fitness...
Muscular fitness...
Physical activity...
Intentional weight loss and mortality...
Meta-analyses of observational studies...
Meta-analyses of randomized controlled trials...
Weight loss via liposuction: impact on cardiovascular risk markers...
Weight loss via bariatric surgery: impact on morbidity and mortality...
Increasing physical activity or cardiorespiratory fitness: consistent reductions in mortality risk...
Does weight loss explain the reduced mortality risk associated with improvements in physical activity or cardiorespiratory fitness?...
Pitfalls of focusing on weight loss: Weight cycling...
Cardiometabolic health improvement: Physical activity vs. weight loss...
Blood pressure...
Glycemic control...
Blood lipids...
Vascular function...
Exercise targets “unhealthy” fat...
Exercise improves “fitness” of adipose tissue...
Healthy obesity phenotype: Importance of cardiorespiratory fitness and physical activity...
Optimization of physical activity and cardiorespiratory fitness...
Summary and conclusions
The increased prevalence of weight loss attempts in the United States has coincided with the increased prevalence of obesity. Thus, a weight-centric approach to obesity treatment and prevention has been largely ineffective. It is unlikely that continued focus on weight loss as the primary metric for success will reverse the trends in obesity prevalence or result in sustainable weight loss. In fact, chronic weight cycling is the norm for millions of adults and is likely to remain so for as long as weight loss persists as the cornerstone of obesity treatment. Weight cycling is associated with health risks that are very similar to those associated with obesity, including higher all-cause mortality risk, and may contribute to weight gain.
A weight-neutral approach to treating obesity-related health conditions may be as, or more, effective than a weight-loss-centered approach, and could avoid pitfalls associated with repeated weight loss failure... Table 1 summarizes the major points in support of a weight-neutral strategy for obesity treatment, which focuses on increasing PA and improving CRF. Such an approach does not assume that obesity is entirely benign, or that there are not circumstances that may necessitate weight loss... However, many obesity-related health conditions are more likely attributable to low PA and CRF rather than obesity per se. Epidemiological studies show that CRF and PA significantly attenuate, and sometimes eliminate, the increased mortality risk associated with obesity. More importantly, increasing PA or CRF is consistently associated with greater reduction in risk of all-cause and CVD mortality than intentional weight loss. In addition, improvements in major cardiometabolic risk markers with exercise training are comparable to those associated with weight loss typically achieved by caloric restriction.
People typically lower their risks of heart disease and premature death far more by gaining fitness than by dropping weight.
Gretchen Reynolds | Sept. 29, 2021
For better health and a longer life span, exercise is more important than weight loss, especially if you are overweight or obese, according to an interesting new review of the relationships between fitness, weight, heart health and longevity. The study, which analyzed the results of hundreds of previous studies of weight loss and workouts in men and women, found that obese people typically lower their risks of heart disease and premature death far more by gaining fitness than by dropping weight or dieting.
Glenn Gaesser, a professor of exercise physiology at Arizona State University in Phoenix,...and his colleague Siddhartha Angadi, a professor of education and kinesiology at the University of Virginia in Charlottesville, began scouring research databases for past studies related to dieting, exercise, fitness, metabolic health and longevity. They were especially interested in meta-analyses, which pool and analyze data from multiple past studies, allowing researchers to look at results from far more people than in most individual studies of weight loss or exercise, which tend to be small-scale.
...As a whole, the studies they cite show that sedentary, obese men and women who begin to exercise and improve their fitness can lower their risk of premature death by as much as 30 percent or more, even if their weight does not budge. This improvement generally puts them at lower risk of early death than people who are considered to be of normal weight but out of shape, Dr. Gaesser said.
On the other hand, if heavy people lose weight by dieting (not illness), their statistical risk of dying young typically drops by about 16 percent, but not in all studies. Some of the research cited in the new review finds that weight loss among obese people does not decrease mortality risks at all.
...people who shed pounds by dieting regained them, then tried again, a yo-yo approach to weight loss that often contributes to metabolic problems like diabetes and high cholesterol and lower life expectancy.
On the other hand, exercise combats those same conditions, (Gaesser) said. It may also, unexpectedly, remake people’s fat stores. “People with obesity usually lose some visceral fat when they exercise,” he said, even if their overall weight loss is negligible. Visceral fat, which collects deep inside our bodies, raises risks for Type 2 diabetes, heart disease and other conditions.
A few of the studies they cite find that exercise likewise alters molecular signaling inside other fat cells in ways that may improve insulin resistance, no matter how much weight someone carries. “It looks like exercise makes fat more fit,” Dr. Gaesser said.
The primary takeaway of the new review, he concluded, is that you do not need to lose weight to be healthy. “You will be better off, in terms of mortality risk, by increasing your physical activity and fitness than by intentionally losing weight,” he said.
https://www.nytimes.com/2021/09/29/well/move/exercise-weight-loss-longer-life.ht...
----------------------------------------------------------------------------
GA Gaesser & SS Angadi. 2021. Obesity treatment: Weight loss versus increasing fitness and physical activity for reducing health risks (Review). Cell. Published:September 20, 2021 DOI:https://doi.org/10.1016/j.isci.2021.102995 https://www.cell.com/iscience/fulltext/S2589-0042(21)00963-9
Summary
We propose a weight-neutral strategy for obesity treatment on the following grounds: (1) the mortality risk associated with obesity is largely attenuated or eliminated by moderate-to-high levels of cardiorespiratory fitness (CRF) or physical activity (PA), (2) most cardiometabolic risk markers associated with obesity can be improved with exercise training independent of weight loss and by a magnitude similar to that observed with weight-loss programs, (3) weight loss, even if intentional, is not consistently associated with lower mortality risk, (4) increases in CRF or PA are consistently associated with greater reductions in mortality risk than is intentional weight loss, and (5) weight cycling is associated with numerous adverse health outcomes including increased mortality. Adherence to PA may improve if health care professionals consider PA and CRF as essential vital signs and consistently emphasize to their patients the myriad benefits of PA and CRF in the absence of weight loss.
Introduction...
The BMI – mortality relationship: Influence of cardiorespiratory fitness and physical activity...
Cardiorespiratory fitness...
Muscular fitness...
Physical activity...
Intentional weight loss and mortality...
Meta-analyses of observational studies...
Meta-analyses of randomized controlled trials...
Weight loss via liposuction: impact on cardiovascular risk markers...
Weight loss via bariatric surgery: impact on morbidity and mortality...
Increasing physical activity or cardiorespiratory fitness: consistent reductions in mortality risk...
Does weight loss explain the reduced mortality risk associated with improvements in physical activity or cardiorespiratory fitness?...
Pitfalls of focusing on weight loss: Weight cycling...
Cardiometabolic health improvement: Physical activity vs. weight loss...
Blood pressure...
Glycemic control...
Blood lipids...
Vascular function...
Exercise targets “unhealthy” fat...
Exercise improves “fitness” of adipose tissue...
Healthy obesity phenotype: Importance of cardiorespiratory fitness and physical activity...
Optimization of physical activity and cardiorespiratory fitness...
Summary and conclusions
The increased prevalence of weight loss attempts in the United States has coincided with the increased prevalence of obesity. Thus, a weight-centric approach to obesity treatment and prevention has been largely ineffective. It is unlikely that continued focus on weight loss as the primary metric for success will reverse the trends in obesity prevalence or result in sustainable weight loss. In fact, chronic weight cycling is the norm for millions of adults and is likely to remain so for as long as weight loss persists as the cornerstone of obesity treatment. Weight cycling is associated with health risks that are very similar to those associated with obesity, including higher all-cause mortality risk, and may contribute to weight gain.
A weight-neutral approach to treating obesity-related health conditions may be as, or more, effective than a weight-loss-centered approach, and could avoid pitfalls associated with repeated weight loss failure... Table 1 summarizes the major points in support of a weight-neutral strategy for obesity treatment, which focuses on increasing PA and improving CRF. Such an approach does not assume that obesity is entirely benign, or that there are not circumstances that may necessitate weight loss... However, many obesity-related health conditions are more likely attributable to low PA and CRF rather than obesity per se. Epidemiological studies show that CRF and PA significantly attenuate, and sometimes eliminate, the increased mortality risk associated with obesity. More importantly, increasing PA or CRF is consistently associated with greater reduction in risk of all-cause and CVD mortality than intentional weight loss. In addition, improvements in major cardiometabolic risk markers with exercise training are comparable to those associated with weight loss typically achieved by caloric restriction.
91margd
Saturated Fatty Acids (SFA)...
Likely cause of Alzheimer’s identified in new study
Hassan Yahaya on September 28, 2021
...Lead study author Dr. John Mamo, Ph.D. — distinguished professor and director of the Curtin Health Innovation Research Institute at Curtin University in Perth, Australia...said...“This study,” he added, “shows that exaggerated abundance in blood of potentially toxic fat-protein complexes can damage microscopic brain blood vessels called capillaries and, thereafter, leak into the brain, causing inflammation and brain cell death...(Changes) in dietary behaviors and certain medications could potentially reduce blood concentration of these toxic fat-protein complexes, (subsequently) reducing the risk for Alzheimer’s or slowing down the disease progression”...
...The researchers found that when the amyloid-beta proteins made in the liver of the test mice combined with fats and traveled to the brain, they interfered with the proper functioning of the brain’s microscopic blood vessels, or capillaries.
This dysfunction in the blood-brain barrier led to the protein-fat complexes leaking from the blood into the brain, resulting in inflammation. This inflammation occurred in both the test group and the control group, but it started at a much younger age in the test group.
...The team also assessed a marker of neurodegeneration and found it to be approximately two times greater in the test mice than in control mice of the same age.
...further studies — especially in humans — are necessary...Nevertheless, understanding how the amyloid-beta-fat complex affects brain capillaries may open up potential medical options to either treat Alzheimer’s disease or slow down the condition’s progression.
https://www.medicalnewstoday.com/articles/likely-cause-of-alzheimers-identified-...
------------------------------------------------------------------------------
Lam V, Takechi R, Hackett MJ, Francis R, Bynevelt M, Celliers LM, et al. (2021) Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype. PLoS Biol 19(9): e3001358. https://doi.org/10.1371/journal.pbio.3001358 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001358
...In contrast, mice fed unsaturated fatty acid–rich diets had no evidence of exaggerated TRL-Aβ secretion and capillary integrity was unremarkable ...The findings of this study and in earlier studies in WT mice on SFA-enriched (Saturated Fatty Acid) diets suggest that chronically exaggerated vascular exposure to TRL-Aβ accelerates age-associated breakdown of cerebral capillaries and the NVU and that this occurs prior to late-stage amyloidogenic pathology being realised...
Likely cause of Alzheimer’s identified in new study
Hassan Yahaya on September 28, 2021
...Lead study author Dr. John Mamo, Ph.D. — distinguished professor and director of the Curtin Health Innovation Research Institute at Curtin University in Perth, Australia...said...“This study,” he added, “shows that exaggerated abundance in blood of potentially toxic fat-protein complexes can damage microscopic brain blood vessels called capillaries and, thereafter, leak into the brain, causing inflammation and brain cell death...(Changes) in dietary behaviors and certain medications could potentially reduce blood concentration of these toxic fat-protein complexes, (subsequently) reducing the risk for Alzheimer’s or slowing down the disease progression”...
...The researchers found that when the amyloid-beta proteins made in the liver of the test mice combined with fats and traveled to the brain, they interfered with the proper functioning of the brain’s microscopic blood vessels, or capillaries.
This dysfunction in the blood-brain barrier led to the protein-fat complexes leaking from the blood into the brain, resulting in inflammation. This inflammation occurred in both the test group and the control group, but it started at a much younger age in the test group.
...The team also assessed a marker of neurodegeneration and found it to be approximately two times greater in the test mice than in control mice of the same age.
...further studies — especially in humans — are necessary...Nevertheless, understanding how the amyloid-beta-fat complex affects brain capillaries may open up potential medical options to either treat Alzheimer’s disease or slow down the condition’s progression.
https://www.medicalnewstoday.com/articles/likely-cause-of-alzheimers-identified-...
------------------------------------------------------------------------------
Lam V, Takechi R, Hackett MJ, Francis R, Bynevelt M, Celliers LM, et al. (2021) Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype. PLoS Biol 19(9): e3001358. https://doi.org/10.1371/journal.pbio.3001358 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001358
...In contrast, mice fed unsaturated fatty acid–rich diets had no evidence of exaggerated TRL-Aβ secretion and capillary integrity was unremarkable ...The findings of this study and in earlier studies in WT mice on SFA-enriched (Saturated Fatty Acid) diets suggest that chronically exaggerated vascular exposure to TRL-Aβ accelerates age-associated breakdown of cerebral capillaries and the NVU and that this occurs prior to late-stage amyloidogenic pathology being realised...
92margd
A biologist I knew ate only raw plant foods after his dad died. The local dentistry school regularly invited him in for students to inspect: apparently his teeth had wear marks typical of our ancient ancestors!
Neanderthals carb loaded, helping grow their big brains
DNA from mouth bacteria suggest human ancestors ate diets rich in starchy plants by 600,000 years ago
Ann Gibbons | 10 May 2021
Here's another blow to the popular image of Neanderthals as brutish meat eaters: A new study of bacteria collected from Neanderthal teeth shows that our close cousins ate so many roots, nuts, or other starchy foods that they dramatically altered the type of bacteria in their mouths. The finding suggests our ancestors had adapted to eating lots of starch by at least 600,000 years ago—about the same time as they needed more sugars to fuel a big expansion of their brains.
The study is "groundbreaking," says Harvard University evolutionary biologist Rachel Carmody, who was not part of the research. The work suggests the ancestors of both humans and Neanderthals were cooking lots of starchy foods at least 600,000 years ago. And they had already adapted to eating more starchy plants long before the invention of agriculture 10,000 years ago, she says...
https://www.science.org/content/article/neanderthals-carb-loaded-helping-grow-th...
Neanderthals carb loaded, helping grow their big brains
DNA from mouth bacteria suggest human ancestors ate diets rich in starchy plants by 600,000 years ago
Ann Gibbons | 10 May 2021
Here's another blow to the popular image of Neanderthals as brutish meat eaters: A new study of bacteria collected from Neanderthal teeth shows that our close cousins ate so many roots, nuts, or other starchy foods that they dramatically altered the type of bacteria in their mouths. The finding suggests our ancestors had adapted to eating lots of starch by at least 600,000 years ago—about the same time as they needed more sugars to fuel a big expansion of their brains.
The study is "groundbreaking," says Harvard University evolutionary biologist Rachel Carmody, who was not part of the research. The work suggests the ancestors of both humans and Neanderthals were cooking lots of starchy foods at least 600,000 years ago. And they had already adapted to eating more starchy plants long before the invention of agriculture 10,000 years ago, she says...
https://www.science.org/content/article/neanderthals-carb-loaded-helping-grow-th...
93margd
Amber L. Alhadeff et al. The power of hunger (essay). Science • 29 Oct 2021 • Vol 374, Issue 6567 • pp. 547-548 •
DOI: 10.1126/science.abl7121 https://www.science.org/doi/10.1126/science.abl7121
...Hunger Filters Perception
...Gut-Brain Signaling and Food Intake
...whereas fat engages vagal (vagus nerve) signaling to inhibit AgRP* neuron activity, the vagus nerve is not required for the inhibition of AgRP neuron activity by glucose... Rather, sugar engages spinal afferent signaling pathways that communicate with hypothalamic hunger neurons... These unexpected findings highlight the role of an understudied gut-brain pathway—spinal afferents**—in nutrient sensing and provide insight into how different nutrients affect our brains and therefore our behavior...
...Bridging the Brain-Periphery Divide
...disentangling...mechanisms (through which the brain interacts with the rest of the body, and vice versa) will aid in the development of targeted therapies for a broad range of human diseases that involve pain and weight control.
* Hypothalamic agouti-related protein (AgRP)–expressing neurons are critical for food intake control in mice and are highly active during food deprivation...notable specificity through which a hypothalamic-to-hindbrain circuit suppresses competing survival behaviors during hunger"
** Spinal afferent neurons are of particular interest because they play the major role in the transduction and transmission of noxious and innocuous stimuli from visceral organs, like the GI tract (to the spinal cord) https://www.sciencedirect.com/topics/neuroscience/afferent-neurons
DOI: 10.1126/science.abl7121 https://www.science.org/doi/10.1126/science.abl7121
...Hunger Filters Perception
...Gut-Brain Signaling and Food Intake
...whereas fat engages vagal (vagus nerve) signaling to inhibit AgRP* neuron activity, the vagus nerve is not required for the inhibition of AgRP neuron activity by glucose... Rather, sugar engages spinal afferent signaling pathways that communicate with hypothalamic hunger neurons... These unexpected findings highlight the role of an understudied gut-brain pathway—spinal afferents**—in nutrient sensing and provide insight into how different nutrients affect our brains and therefore our behavior...
...Bridging the Brain-Periphery Divide
...disentangling...mechanisms (through which the brain interacts with the rest of the body, and vice versa) will aid in the development of targeted therapies for a broad range of human diseases that involve pain and weight control.
* Hypothalamic agouti-related protein (AgRP)–expressing neurons are critical for food intake control in mice and are highly active during food deprivation...notable specificity through which a hypothalamic-to-hindbrain circuit suppresses competing survival behaviors during hunger"
** Spinal afferent neurons are of particular interest because they play the major role in the transduction and transmission of noxious and innocuous stimuli from visceral organs, like the GI tract (to the spinal cord) https://www.sciencedirect.com/topics/neuroscience/afferent-neurons
94margd
Also posted on COVID thread (25):
Diet-related diseases pose a major risk for Covid-19. But the U.S. overlooks them.
Other countries have been galvanized to confront diet issues. The U.S. has had no such wakeup call.
HELENA BOTTEMILLER EVICH | 10/31/2021
https://www.politico.com/news/2021/10/31/covid-deaths-diet-diseases-nutrition-am...
Diet-related diseases pose a major risk for Covid-19. But the U.S. overlooks them.
Other countries have been galvanized to confront diet issues. The U.S. has had no such wakeup call.
HELENA BOTTEMILLER EVICH | 10/31/2021
https://www.politico.com/news/2021/10/31/covid-deaths-diet-diseases-nutrition-am...
95margd
Related?
Multivitamins, but Not Cocoa, Tied to Slowed Brain Aging
Pauline Anderson | November 11, 2021
Taking a daily multivitamin for 3 years is associated with a 60% slowing of cognitive aging, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.
In addition to testing the effect of a daily multivitamin on cognition the COSMOS-Mind study also examined the effect of cocoa flavanols, but showed no beneficial effect...
https://www.medscape.com/viewarticle/962772
(margd: access is free but you have to create account. I've had one for years.)
Multivitamins, but Not Cocoa, Tied to Slowed Brain Aging
Pauline Anderson | November 11, 2021
Taking a daily multivitamin for 3 years is associated with a 60% slowing of cognitive aging, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.
In addition to testing the effect of a daily multivitamin on cognition the COSMOS-Mind study also examined the effect of cocoa flavanols, but showed no beneficial effect...
https://www.medscape.com/viewarticle/962772
(margd: access is free but you have to create account. I've had one for years.)
96jjwilson61
>95 margd: Did they control for the possibility that people who take multivitamins might less healthy than average?
97margd
>96 jjwilson61: Sounds like test groups were balanced -- assigned by computer based on demographics, diabetes, alcohol use, etc.--and prior multivitamin use.
98margd
Related?
Olive Oil Reduces Both Total and Cause-specific Mortality
Jan 12, 2022
Pooled analysis of Nurses’ Health, Health Professionals Follow-up Studies shows many benefits
...Eating more olive oil can lower the risk of total and cause-specific mortality, according to a recent analysis of data from two large, well-known studies. And, replacing other fats such as margarine, butter, mayonnaise, and dairy fat with olive oil was associated with a lower risk of mortality
...Compared with participants who never or rarely consumed olive oil, among those with the highest consumption of olive oil—defined as >0.5 tablespoons/day or >7 margd: g/d—the multivariable-adjusted pooled hazard ratio (HR) for all-cause mortality was 0.81 (95% CI: 0.78-0.84).
Researchers also found that a higher intake of olive oil was associated with:
A 19% lower risk of death from CVD (HR: 0.81; 95% CI: 0.75-0.87).
A 17% lower risk of death from cancer (HR: 0.83; 95% CI: 0.78-0.89).
A 29% lower risk of death from a neurodegenerative disease.
An 18% lower risk of death from a respiratory disease.
Hu and fellow researchers also did a substitution analysis, in which they replaced 10 g/d of margarine, butter, mayonnaise, and dairy fat with equivalent amounts of olive oil. This replacement resulted in an 8%-34% lower risk of total and cause-specific mortality.
They found no significant associations in comparisons of olive oil with other vegetable oils combined...
https://www.physiciansweekly.com/olive-oil-reduces-both-total-and-cause-specific...
------------------------------------------------------------
Marta Guasch-Ferré et al. 2022. Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults (Original Investigation). Journal of the American College of Cardiology Volume 79, Issue 2, 18 January 2022, Pages 101-112 https://doi.org/10.1016/j.jacc.2021.10.041 https://www.sciencedirect.com/science/article/abs/pii/S0735109721081481?via%3Dih...
-------------------------------------------------------------
Susanna C.Larsson. 2022. Can Small Amounts of Olive Oil Keep the Death Away? (Editorial Comment). Journal of the American College of Cardiology Volume 79, Issue 2, 18 January 2022, Pages 113-115. https://doi.org/10.1016/j.jacc.2021.11.006 https://www.sciencedirect.com/science/article/abs/pii/S073510972108147X
Olive Oil Reduces Both Total and Cause-specific Mortality
Jan 12, 2022
Pooled analysis of Nurses’ Health, Health Professionals Follow-up Studies shows many benefits
...Eating more olive oil can lower the risk of total and cause-specific mortality, according to a recent analysis of data from two large, well-known studies. And, replacing other fats such as margarine, butter, mayonnaise, and dairy fat with olive oil was associated with a lower risk of mortality
...Compared with participants who never or rarely consumed olive oil, among those with the highest consumption of olive oil—defined as >0.5 tablespoons/day or >7 margd: g/d—the multivariable-adjusted pooled hazard ratio (HR) for all-cause mortality was 0.81 (95% CI: 0.78-0.84).
Researchers also found that a higher intake of olive oil was associated with:
A 19% lower risk of death from CVD (HR: 0.81; 95% CI: 0.75-0.87).
A 17% lower risk of death from cancer (HR: 0.83; 95% CI: 0.78-0.89).
A 29% lower risk of death from a neurodegenerative disease.
An 18% lower risk of death from a respiratory disease.
Hu and fellow researchers also did a substitution analysis, in which they replaced 10 g/d of margarine, butter, mayonnaise, and dairy fat with equivalent amounts of olive oil. This replacement resulted in an 8%-34% lower risk of total and cause-specific mortality.
They found no significant associations in comparisons of olive oil with other vegetable oils combined...
https://www.physiciansweekly.com/olive-oil-reduces-both-total-and-cause-specific...
------------------------------------------------------------
Marta Guasch-Ferré et al. 2022. Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults (Original Investigation). Journal of the American College of Cardiology Volume 79, Issue 2, 18 January 2022, Pages 101-112 https://doi.org/10.1016/j.jacc.2021.10.041 https://www.sciencedirect.com/science/article/abs/pii/S0735109721081481?via%3Dih...
-------------------------------------------------------------
Susanna C.Larsson. 2022. Can Small Amounts of Olive Oil Keep the Death Away? (Editorial Comment). Journal of the American College of Cardiology Volume 79, Issue 2, 18 January 2022, Pages 113-115. https://doi.org/10.1016/j.jacc.2021.11.006 https://www.sciencedirect.com/science/article/abs/pii/S073510972108147X
99margd
Lars T. Fadnes et a. 2022. Estimating impact of food choices on life expectancy: A modeling study. PLOS Medicine Published: February 8, 2022. https://doi.org/10.1371/journal.pmed.1003889 https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003889
Abstract
Background
Interpreting and utilizing the findings of nutritional research can be challenging to clinicians, policy makers, and even researchers. To make better decisions about diet, innovative methods that integrate best evidence are needed. We have developed a decision support model that predicts how dietary choices affect life expectancy (LE).
Methods and findings
Based on meta-analyses and data from the Global Burden of Disease study (2019), we used life table methodology to estimate how LE changes with sustained changes in the intake of fruits, vegetables, whole grains, refined grains, nuts, legumes, fish, eggs, milk/dairy, red meat, processed meat, and sugar-sweetened beverages. We present estimates (with 95% uncertainty intervals 95% UIs) for an optimized diet and a feasibility approach diet. An optimal diet had substantially higher intake than a typical diet of whole grains, legumes, fish, fruits, vegetables, and included a handful of nuts, while reducing red and processed meats, sugar-sweetened beverages, and refined grains. A feasibility approach diet was a midpoint between an optimal and a typical Western diet. A sustained change from a typical Western diet to the optimal diet from age 20 years would increase LE by more than a decade for women from the United States (10.7 ... years) and men (13.0 ... years). The largest gains would be made by eating
more legumes (females: 2.2 ...; males: 2.5 ...),
more whole grains (females: 2.0 ...; males: 2.3... ), and
more nuts (females: 1.7 ...; males: 2.0 ...), and
less red meat (females: 1.6... ; males: 1.9 ...) and
less processed meat (females: 1.6 ...; males: 1.9 ...).
Changing from a typical diet to the optimized diet at age 60 years would increase LE by 8.0 ... years for women and 8.8 ... years for men, and 80-year-olds would gain 3.4 years (...females: 2.6 to 3.8/males: 2.7 to 3.9). Change from typical to feasibility approach diet would increase LE by 6.2 ... years for 20-year-old women from the United States and 7.3 ... years for men. Using NutriGrade, the overall quality of evidence was assessed as moderate. The methodology provides population estimates under given assumptions and is not meant as individualized forecasting, with study limitations that include uncertainty for time to achieve full effects, the effect of eggs, white meat, and oils, individual variation in protective and risk factors, uncertainties for future development of medical treatments; and changes in lifestyle.
Conclusions
A sustained dietary change may give substantial health gains for people of all ages both for optimized and feasible changes. Gains are predicted to be larger the earlier the dietary changes are initiated in life. The Food4HealthyLife calculator that we provide online could be useful for clinicians, policy makers, and laypeople to understand the health impact of dietary choices.
Graph--increase in life expectancy v age at diet change per element of optimal diet
( https://twitter.com/EricTopol/status/1492568529354117121/photo/1 )
Abstract
Background
Interpreting and utilizing the findings of nutritional research can be challenging to clinicians, policy makers, and even researchers. To make better decisions about diet, innovative methods that integrate best evidence are needed. We have developed a decision support model that predicts how dietary choices affect life expectancy (LE).
Methods and findings
Based on meta-analyses and data from the Global Burden of Disease study (2019), we used life table methodology to estimate how LE changes with sustained changes in the intake of fruits, vegetables, whole grains, refined grains, nuts, legumes, fish, eggs, milk/dairy, red meat, processed meat, and sugar-sweetened beverages. We present estimates (with 95% uncertainty intervals 95% UIs) for an optimized diet and a feasibility approach diet. An optimal diet had substantially higher intake than a typical diet of whole grains, legumes, fish, fruits, vegetables, and included a handful of nuts, while reducing red and processed meats, sugar-sweetened beverages, and refined grains. A feasibility approach diet was a midpoint between an optimal and a typical Western diet. A sustained change from a typical Western diet to the optimal diet from age 20 years would increase LE by more than a decade for women from the United States (10.7 ... years) and men (13.0 ... years). The largest gains would be made by eating
more legumes (females: 2.2 ...; males: 2.5 ...),
more whole grains (females: 2.0 ...; males: 2.3... ), and
more nuts (females: 1.7 ...; males: 2.0 ...), and
less red meat (females: 1.6... ; males: 1.9 ...) and
less processed meat (females: 1.6 ...; males: 1.9 ...).
Changing from a typical diet to the optimized diet at age 60 years would increase LE by 8.0 ... years for women and 8.8 ... years for men, and 80-year-olds would gain 3.4 years (...females: 2.6 to 3.8/males: 2.7 to 3.9). Change from typical to feasibility approach diet would increase LE by 6.2 ... years for 20-year-old women from the United States and 7.3 ... years for men. Using NutriGrade, the overall quality of evidence was assessed as moderate. The methodology provides population estimates under given assumptions and is not meant as individualized forecasting, with study limitations that include uncertainty for time to achieve full effects, the effect of eggs, white meat, and oils, individual variation in protective and risk factors, uncertainties for future development of medical treatments; and changes in lifestyle.
Conclusions
A sustained dietary change may give substantial health gains for people of all ages both for optimized and feasible changes. Gains are predicted to be larger the earlier the dietary changes are initiated in life. The Food4HealthyLife calculator that we provide online could be useful for clinicians, policy makers, and laypeople to understand the health impact of dietary choices.
Graph--increase in life expectancy v age at diet change per element of optimal diet
( https://twitter.com/EricTopol/status/1492568529354117121/photo/1 )
100margd
"(Researchers) did find that the higher the concentration of vitamin A (metabolite) over a long period of time, the more likely people were to live longer. Plus, the link was causal, meaning that, rather than people with more vitamin A just happening to live longer for some other reason, the vitamin actually had an effect on their longevity...fruits and vegetables that are good sources of carotenoids like leafy greens, bell peppers, carrots, and sweet potatoes."
https://www.eatthis.com/news-vitamin-could-lengthen-life/
----------------------------------------------------------------------
"Specifically, a 10-fold increase in retinol metabolite was causally associated with 7% higher odds of longevity"
"our findings did not rule out the favorable roles of fruit and vegetables, which contain numerous micronutrients and fibers besides the abovementioned antioxidants"
"higher circulating lycopene, selenium, β-carotene, and vitamin C concentrations might still be beneficial in discriminatingly selected populations who have risk factors at baseline or under increased oxidative stress status."
"our findings are only generalizable to individuals of European descent"
Zhimin Yu, Fangfang Zhang, Chengkai Xu, Yanggan Wang, "Association between Circulating Antioxidants and Longevity: Insight from Mendelian Randomization Study", BioMed Research International, vol. 2022, Article ID 4012603, 14 pages, 2022. https://doi.org/10.1155/2022/4012603 https://www.hindawi.com/journals/bmri/2022/4012603/
Abstract
Background. Antioxidants attracted long-standing attention as promising preventive agents worldwide. Previous observational studies have reported that circulating antioxidants are associated with reduced mortality; however, randomized clinical trials indicate neutral or harmful impacts. The association of long-term circulating antioxidant exposure with longevity is still unclear.
Objectives. We aim to determine whether long-term circulating antioxidant exposure is causally associated with longevity in the general population using the two-sample Mendelian randomization (MR) design.
Methods. Genetic instruments for circulating antioxidants (ascorbate, lycopene, selenium, beta-carotene, and retinol) and antioxidant metabolites (ascorbate, alpha-tocopherol, gamma-tocopherol, and retinol) were identified from the largest up-to-date genome-wide association studies (GWASs). Summary statistics of these instruments with individual survival to the 90th vs. 60th percentile age (11,262 cases and 25,483 controls) and parental lifespan (individuals) were extracted. The causal effect was estimated using the inverse-variance weighted method in the main analysis and complemented by multiple sensitivity analyses to test the robustness of results.
Results. We found that genetically determined higher concentration of circulating retinol (vitamin A) metabolite was casually associated with a higher odds of longevity (OR, 1.07... ) and increased parental lifespan (lifespan years per 10-fold increase: 0.17... ). Present evidence did not support a causal impact of circulating ascorbate (vitamin C), tocopherol (vitamin E), lycopene, selenium or beta-carotene on life expectancy. No evidence was identified to show the pleiotropic effects had biased the results.
Conclusions. Long-term higher exposure to retinol metabolite is causally associated with longevity in the general population. Future MR analyses could assess the current findings further by utilizing additional genetic variants and greater samples from large-scale GWASs.
... 3. Results
3.2. Circulating Antioxidant Metabolites and Longevity
...Specifically, a 10-fold increase in retinol metabolite was causally associated with 7% higher odds of longevity...
4. Discussion
4.1. Principal findings
...our findings did not rule out the favorable roles of fruit and vegetables, which contain numerous micronutrients and fibers besides the abovementioned antioxidants.
...4.3. Strengths and Limitations
A major strength of the present study was the use of two-sample MR Mendelian randomization design, which overcomes the short duration of antioxidant exposure in RCTs and minimizes potential confounding bias in observational investigations and adds to the body of knowledge on dietary antioxidants and longevity. Another strength was that we used two European datasets with large sample size (>1 margd: million) for SNP-longevity single nucleotide polymorphism associations in this MR analysis. Thus, we had adequate statistical power to identify even modest causal associations for most analyses...
Our study also has several limitations which merit further consideration.
First, individuals had to survive to a certain age to be recruited in the longevity GWASs. As a consequence, individuals with early death were missing from the control group, and the true effect might be underestimated if those individuals have more unfavorable risk factors.
Second, we are unable to evaluate nonlinearity in the associations of circulating antioxidants with life expectancy that have previously been suggested, in particular for circulating lycopene 68. Future investigations utilizing individual-level data to fully clarify the potential dose-response associations are still needed.
Third, higher circulating lycopene, selenium, β-carotene, and vitamin C concentrations might still be beneficial in discriminatingly selected populations who have risk factors at baseline or under increased oxidative stress status. For instance, protective effects of circulating β-carotene and selenium on mortality have been demonstrated to be more obvious in individuals aged above 60 years when compared with younger individuals 68. However, our study could not evaluate the effect of these antioxidants on longevity in subgroups with different risk factors or lacking certain kind of nutrients where antioxidant supplement appears to be more beneficial.
Finally, our findings are only generalizable to individuals of European descent.
https://www.eatthis.com/news-vitamin-could-lengthen-life/
----------------------------------------------------------------------
"Specifically, a 10-fold increase in retinol metabolite was causally associated with 7% higher odds of longevity"
"our findings did not rule out the favorable roles of fruit and vegetables, which contain numerous micronutrients and fibers besides the abovementioned antioxidants"
"higher circulating lycopene, selenium, β-carotene, and vitamin C concentrations might still be beneficial in discriminatingly selected populations who have risk factors at baseline or under increased oxidative stress status."
"our findings are only generalizable to individuals of European descent"
Zhimin Yu, Fangfang Zhang, Chengkai Xu, Yanggan Wang, "Association between Circulating Antioxidants and Longevity: Insight from Mendelian Randomization Study", BioMed Research International, vol. 2022, Article ID 4012603, 14 pages, 2022. https://doi.org/10.1155/2022/4012603 https://www.hindawi.com/journals/bmri/2022/4012603/
Abstract
Background. Antioxidants attracted long-standing attention as promising preventive agents worldwide. Previous observational studies have reported that circulating antioxidants are associated with reduced mortality; however, randomized clinical trials indicate neutral or harmful impacts. The association of long-term circulating antioxidant exposure with longevity is still unclear.
Objectives. We aim to determine whether long-term circulating antioxidant exposure is causally associated with longevity in the general population using the two-sample Mendelian randomization (MR) design.
Methods. Genetic instruments for circulating antioxidants (ascorbate, lycopene, selenium, beta-carotene, and retinol) and antioxidant metabolites (ascorbate, alpha-tocopherol, gamma-tocopherol, and retinol) were identified from the largest up-to-date genome-wide association studies (GWASs). Summary statistics of these instruments with individual survival to the 90th vs. 60th percentile age (11,262 cases and 25,483 controls) and parental lifespan (individuals) were extracted. The causal effect was estimated using the inverse-variance weighted method in the main analysis and complemented by multiple sensitivity analyses to test the robustness of results.
Results. We found that genetically determined higher concentration of circulating retinol (vitamin A) metabolite was casually associated with a higher odds of longevity (OR, 1.07... ) and increased parental lifespan (lifespan years per 10-fold increase: 0.17... ). Present evidence did not support a causal impact of circulating ascorbate (vitamin C), tocopherol (vitamin E), lycopene, selenium or beta-carotene on life expectancy. No evidence was identified to show the pleiotropic effects had biased the results.
Conclusions. Long-term higher exposure to retinol metabolite is causally associated with longevity in the general population. Future MR analyses could assess the current findings further by utilizing additional genetic variants and greater samples from large-scale GWASs.
... 3. Results
3.2. Circulating Antioxidant Metabolites and Longevity
...Specifically, a 10-fold increase in retinol metabolite was causally associated with 7% higher odds of longevity...
4. Discussion
4.1. Principal findings
...our findings did not rule out the favorable roles of fruit and vegetables, which contain numerous micronutrients and fibers besides the abovementioned antioxidants.
...4.3. Strengths and Limitations
A major strength of the present study was the use of two-sample MR Mendelian randomization design, which overcomes the short duration of antioxidant exposure in RCTs and minimizes potential confounding bias in observational investigations and adds to the body of knowledge on dietary antioxidants and longevity. Another strength was that we used two European datasets with large sample size (>1 margd: million) for SNP-longevity single nucleotide polymorphism associations in this MR analysis. Thus, we had adequate statistical power to identify even modest causal associations for most analyses...
Our study also has several limitations which merit further consideration.
First, individuals had to survive to a certain age to be recruited in the longevity GWASs. As a consequence, individuals with early death were missing from the control group, and the true effect might be underestimated if those individuals have more unfavorable risk factors.
Second, we are unable to evaluate nonlinearity in the associations of circulating antioxidants with life expectancy that have previously been suggested, in particular for circulating lycopene 68. Future investigations utilizing individual-level data to fully clarify the potential dose-response associations are still needed.
Third, higher circulating lycopene, selenium, β-carotene, and vitamin C concentrations might still be beneficial in discriminatingly selected populations who have risk factors at baseline or under increased oxidative stress status. For instance, protective effects of circulating β-carotene and selenium on mortality have been demonstrated to be more obvious in individuals aged above 60 years when compared with younger individuals 68. However, our study could not evaluate the effect of these antioxidants on longevity in subgroups with different risk factors or lacking certain kind of nutrients where antioxidant supplement appears to be more beneficial.
Finally, our findings are only generalizable to individuals of European descent.
101margd
Aaron M. Cypess et al. 2022. Reassessing Human Adipose Tissue (Review). N Engl J Med 24 Feb 2022; 386:768-779 DOI: 10.1056/NEJMra2032804 https://www.nejm.org/doi/full/10.1056/NEJMra2032804
Adipose tissue is an underappreciated and misunderstood organ. Capable of more than doubling in mass and then returning to baseline,1 white adipose tissue (WAT) continues to play an essential role in the development of humans. WAT efficiently stores sufficient energy to free us from constantly seeking food, permitting us to devote our physical and mental efforts toward building civilization. Brown adipose tissue (BAT) consumes glucose and triglycerides, generating heat. An organ designed for nonshivering thermogenesis, BAT has enabled mammals to thrive in the current Cenozoic era. Once thought to be physiologically irrelevant in adult humans, long-term activation of BAT has been hypothesized to contribute to wide-ranging health benefits in tissues as diverse as the gastrointestinal, cardiovascular, and musculoskeletal systems.2 Highlighting the developments from the past 5 to 10 years, this review discusses the two principal facets of human adipose tissue: its functional roles related to triglyceride storage, as well as its excess in obesity, and its far-reaching, complementary physiological roles in the endocrine system.
(1) Structure and Distribution of Adipose-Tissue Depots...
(2) Function and Communication...
(3) Obesity as a Complication of Too Much WAT
The overweight and obesity pandemics affect more than 70% of the U.S. population59 and are projected to increase in prevalence over the next 30 years.60 In parallel, there has been a rise in obesity-related conditions such as type 2 diabetes, precocious puberty, cardiovascular disease, and several cancers.61 Even more troubling is the observation that the rates of obesity are increasing much faster among children than among adults and that obese children are more likely to become obese adults at high risk for severe health complications (Figure 3).62 Adequate responses to the clinical and societal sequelae of these trends require a more accurate understanding of the specific effects of the different WAT and BAT depots. Current assessments across adult and pediatric populations often use BMI exclusively, which, at minimum, requires adjustments for age, sex, and genetic and ethnic backgrounds.63 BMI cannot provide information about WAT distribution or the predispositions of specific depots for their distinctive pathophysiology or the likelihood of a response to targeted therapies. Going forward, it will be particularly important to conduct large studies of epidemiologic trends that go beyond BMI and incorporate other estimates of the distribution of WAT depots, including waist circumference,64 in order to better understand the role of WAT distribution in obesity-related metabolic disease.
Although it is correct to attribute the increasing rates of obesity to excessive triglyceride storage in WAT, that picture is too simplistic and impedes the development of treatment strategies. Since the start of the obesity pandemic in the 1970s, the principal contributing causes and their individual influence remain unknown. The roles of portion sizes, specific food classes, particular ingredients, and changes in patterns of activity are being investigated.65 Concomitantly, it is useful to conceptualize obesity as a disease of the brain that is manifested as an excess of WAT and dysfunctional BAT. Studies have shown the pernicious cycles that accelerate the development of obesity once a person has begun to gain weight.66 The hypothalamic region of the brain is of increasing interest because it integrates multiple physiological signals from the body, transmits them to different brain regions, and coordinates the regulation of diverse processes, including body temperature and feeding. Studies in rodents have mapped the neuronal pathways that interpret signals from feeding and from the WAT itself regarding its mass and then integrate those signals into homeostatic and hedonic messages, which interpret the availability of energy stores and the emotional meaning of specific foods, respectively.67 Besides the WAT, obesity also disrupts the ability of the hypothalamus to stimulate BAT energy expenditure.67 Obesity cannot be viewed simply as a failure of willpower. Instead, it is a complex interplay among hundreds of genes, socioeconomic demands, and personal decision making that ultimately leads to a long-term increase in average caloric intake over energy expenditure.68
Connections among obesity, its metabolic complications, and genetic influences have become more established through genomewide association studies. These large-scale global population studies have identified new genetic loci in the central nervous system, indicating a potentially genetic component of aspects of lifestyle, as well as insulin resistance, linking central obesity to metabolic dysregulation and, ultimately, the risk of cardiovascular disease.69 However, it is critical to appreciate the distinction between the heritability of obesity and the effect of any one gene. Genetic influences on obesity are substantial, up to 70% on the basis of studies involving populations of predominantly European origin,70,71 but this strong effect should not be misinterpreted to mean that there is a single “fat gene.” Currently, only 20% of the entire phenotypic variation in obesity can be explained by the thousands of loci identified so far.72 Adding further complexity is the effect of epigenetics — heritable yet reversible changes in gene function that do not involve the DNA code itself. Obesity and even dietary components can have profound phenotypic effects.73 Efforts are now being focused on how the mechanisms by which the genes and the associated physiological pathways affect short- and long-term energy imbalances and the subsequent health complications.
How does excess adipose tissue lead to disease? Like no other cells, white adipocytes are adept at enlarging and can swell from a diameter of 30 to 40 μm to more than 100 μm, an increase in volume by a factor of more than 10. Starting in early adulthood, lean U.S. adults spend the next decades challenging their adipocytes by gaining on average 0.5 kg (1.1 lb) per year, with even higher weight increases among the overweight and obese,74 putting an enormous demand on the WAT depots to store triglycerides by the fifth and sixth decades of life.75
Anatomical location and genetics largely determine the proportional increase in adipocyte size and number and the physiological responses. For example, people whose subcutaneous depots maintain smaller adipocytes have fewer metabolic complications.31 Furthermore, in people who are genetically predisposed to impaired catecholamine-mediated lipolysis, white adipocytes become very large,32 a situation exacerbated by a genetic inability to recruit new adipocytes.76 As obesity progresses, preadipocyte differentiation becomes dysfunctional, leading to reduced insulin signaling, glucose uptake, and adiponectin release by the mature adipocytes.77,78 Ultimately, hypertrophic WAT growth and expansion restrict the ability of oxygen to diffuse from the capillaries into the adipocytes.77 This hypoxia constitutes a biologic red alert for the cells, altering the expression of more than 1000 genes and triggering a series of interconnected responses that ultimately lead to local resistance to both insulin and adrenergic signaling, increased inflammation, and cellular damage. Failure of the adipose tissue to continue expanding leads to overflow and subsequent deposition of triglycerides throughout the body, with ectopic accumulation in the liver and skeletal muscle. The extent of this lipotoxicity is an important determinant of the development of metabolic dysregulation, type 2 diabetes, and cardiovascular disease.79
This milieu leads to immune-system dysfunction and is thought to contribute to increased morbidity and mortality from infectious disease, currently highlighted by the worrisome epidemiologic reports about people with obesity and coronavirus disease 2019.80 Obesity is also associated with an increased risk of many types of cancer, including cancer of the breast, uterus, ovary, esophagus, stomach, colon or rectum, liver, gallbladder, pancreas, kidney, thyroid, and meninges, as well as multiple myeloma,81 but the precise mechanisms are currently unclear. Three causative agents identified so far are hyperinsulinemia, factors released during chronic inflammation, and increased estrogen production. Given the scope of disorders, the question that arises is whether excess stored triglycerides are ever benign. A metabolically healthy obese phenotype has been postulated, which has been associated with several aspects of adipocyte function, such as the release of specific adipokines.82 Whether obese persons who are metabolically healthy are nevertheless on an inexorable path toward metabolic disease remains to be determined.83
(4) Treatments for Overweight and Obesity
There are three ways to achieve a net negative energy balance: reduce food consumption, reduce nutrient absorption, and increase energy expenditure. All three ultimately converge on the common goal of reducing WAT triglyceride content. Pharmacotherapy aimed at these different pathways has been extensively reviewed.84 Several treatments currently approved by the Food and Drug Administration for the treatment of obesity directly involve adipose tissues. For example, glucagon-like peptide 1 receptor agonists such as liraglutide cause weight loss by means of appetite inhibition and are even more effective with exercise,85 yet their beneficial effects may also be mediated by stimulation of WAT lipolysis and BAT thermogenesis.86 Potential new therapies focusing on adipose tissue include bimagrumab, an inhibitor of the activin type II receptor, which reduces WAT mass while increasing the growth of skeletal muscle.87 The most effective approach to weight loss that also results in metabolic improvements is bariatric surgery.88 Although these operations reduce the complications of obesity through multiple mechanisms, much of the effectiveness is due to the profound loss of WAT mass.89 Current studies are determining the mechanisms by which weight loss is achieved, the long-term adverse effects, and the durability of the various surgical interventions.
There is also the direct approach of removing adipose tissue, but as intimated above, resecting the wrong adipose-tissue depot could worsen the metabolic effect. Noncosmetic liposuction of subcutaneous fat does not lead to long-term weight loss or improved health.90 Also, it is essential to retain at least a modicum of adipose tissue. The lipodystrophic syndromes associated with human immunodeficiency virus infection and medications used to treat it, as well as more rare genetic syndromes, have shown that too little WAT leads to lipotoxic metabolic dysfunction and leptin-deficient reproductive dysfunction.91,92 In certain circumstances, it is even beneficial to increase adipose tissue mass. Thiazolidinediones are medications that treat diabetes by activating the nuclear receptor PPAR-γ (peroxisome proliferator–activated receptor γ) and increasing the number of smaller and more insulin-responsive adipocytes that can more safely store triglycerides.93 By inducing hyperplasia instead of hypertrophy, thiazolidinediones lead to a paradoxical improvement in a patient’s metabolic profile while increasing adipocyte mass.
Could long-term BAT activation help treat obesity or related metabolic diseases? In rodents, the answer is unequivocally yes,94 but in humans, the answer has yet to be determined. As already discussed, humans have proportionally less BAT than smaller mammals, but contemporary humans may have even less BAT than is required to support their physiological and metabolic needs. BAT mass dramatically decreases with increased ambient temperatures,95 and aging also appears to induce BAT atrophy,96 raising the possibility that contemporary humans who create a thermoneutral environment are artificially lowering their BAT mass and its contribution to energy balance and metabolic health. Even the limited BAT present in adults appears to have a substantial clinical effect, because retrospective and prospective studies show an inverse association between BAT activity and BMI.97 In addition, a recent study showed that persons with BAT had healthier blood glucose, triglyceride, and high-density lipoprotein levels than persons without BAT.2 Those with BAT had a lower prevalence of cardiometabolic diseases such as type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure, and hypertension.
Clinical trials are necessary to determine the outcomes from long-term BAT activation, given that studies in rodents suggest that activating BAT could lead to compensatory food intake98 or the opposite, suppression of appetite.99 Initial prospective clinical studies have shown that long-term treatment with β3-adrenergic receptor agonists increases BAT mass and browning of WAT and is associated with improvements in insulin sensitivity and cardiometabolic risk factors.100
(5) Conclusions
The riskiest approach to human adipose tissue is to dismiss its importance. WAT lies at the heart of the obesity pandemic, and its response to excess calories has an effect on every organ system, with profound effects on morbidity and mortality worldwide. The past decade, and particularly the past 5 years, has seen an explosive growth in our understanding of adipose tissue, with work that recognizes human WAT and BAT as organs that have anatomical, functional, and genetic diversity. Going forward, fat will ideally be appreciated for what it is, a polychromatic tissue, which is as relevant and influential as other organs for sustaining human health.
Adipose tissue is an underappreciated and misunderstood organ. Capable of more than doubling in mass and then returning to baseline,1 white adipose tissue (WAT) continues to play an essential role in the development of humans. WAT efficiently stores sufficient energy to free us from constantly seeking food, permitting us to devote our physical and mental efforts toward building civilization. Brown adipose tissue (BAT) consumes glucose and triglycerides, generating heat. An organ designed for nonshivering thermogenesis, BAT has enabled mammals to thrive in the current Cenozoic era. Once thought to be physiologically irrelevant in adult humans, long-term activation of BAT has been hypothesized to contribute to wide-ranging health benefits in tissues as diverse as the gastrointestinal, cardiovascular, and musculoskeletal systems.2 Highlighting the developments from the past 5 to 10 years, this review discusses the two principal facets of human adipose tissue: its functional roles related to triglyceride storage, as well as its excess in obesity, and its far-reaching, complementary physiological roles in the endocrine system.
(1) Structure and Distribution of Adipose-Tissue Depots...
(2) Function and Communication...
(3) Obesity as a Complication of Too Much WAT
The overweight and obesity pandemics affect more than 70% of the U.S. population59 and are projected to increase in prevalence over the next 30 years.60 In parallel, there has been a rise in obesity-related conditions such as type 2 diabetes, precocious puberty, cardiovascular disease, and several cancers.61 Even more troubling is the observation that the rates of obesity are increasing much faster among children than among adults and that obese children are more likely to become obese adults at high risk for severe health complications (Figure 3).62 Adequate responses to the clinical and societal sequelae of these trends require a more accurate understanding of the specific effects of the different WAT and BAT depots. Current assessments across adult and pediatric populations often use BMI exclusively, which, at minimum, requires adjustments for age, sex, and genetic and ethnic backgrounds.63 BMI cannot provide information about WAT distribution or the predispositions of specific depots for their distinctive pathophysiology or the likelihood of a response to targeted therapies. Going forward, it will be particularly important to conduct large studies of epidemiologic trends that go beyond BMI and incorporate other estimates of the distribution of WAT depots, including waist circumference,64 in order to better understand the role of WAT distribution in obesity-related metabolic disease.
Although it is correct to attribute the increasing rates of obesity to excessive triglyceride storage in WAT, that picture is too simplistic and impedes the development of treatment strategies. Since the start of the obesity pandemic in the 1970s, the principal contributing causes and their individual influence remain unknown. The roles of portion sizes, specific food classes, particular ingredients, and changes in patterns of activity are being investigated.65 Concomitantly, it is useful to conceptualize obesity as a disease of the brain that is manifested as an excess of WAT and dysfunctional BAT. Studies have shown the pernicious cycles that accelerate the development of obesity once a person has begun to gain weight.66 The hypothalamic region of the brain is of increasing interest because it integrates multiple physiological signals from the body, transmits them to different brain regions, and coordinates the regulation of diverse processes, including body temperature and feeding. Studies in rodents have mapped the neuronal pathways that interpret signals from feeding and from the WAT itself regarding its mass and then integrate those signals into homeostatic and hedonic messages, which interpret the availability of energy stores and the emotional meaning of specific foods, respectively.67 Besides the WAT, obesity also disrupts the ability of the hypothalamus to stimulate BAT energy expenditure.67 Obesity cannot be viewed simply as a failure of willpower. Instead, it is a complex interplay among hundreds of genes, socioeconomic demands, and personal decision making that ultimately leads to a long-term increase in average caloric intake over energy expenditure.68
Connections among obesity, its metabolic complications, and genetic influences have become more established through genomewide association studies. These large-scale global population studies have identified new genetic loci in the central nervous system, indicating a potentially genetic component of aspects of lifestyle, as well as insulin resistance, linking central obesity to metabolic dysregulation and, ultimately, the risk of cardiovascular disease.69 However, it is critical to appreciate the distinction between the heritability of obesity and the effect of any one gene. Genetic influences on obesity are substantial, up to 70% on the basis of studies involving populations of predominantly European origin,70,71 but this strong effect should not be misinterpreted to mean that there is a single “fat gene.” Currently, only 20% of the entire phenotypic variation in obesity can be explained by the thousands of loci identified so far.72 Adding further complexity is the effect of epigenetics — heritable yet reversible changes in gene function that do not involve the DNA code itself. Obesity and even dietary components can have profound phenotypic effects.73 Efforts are now being focused on how the mechanisms by which the genes and the associated physiological pathways affect short- and long-term energy imbalances and the subsequent health complications.
How does excess adipose tissue lead to disease? Like no other cells, white adipocytes are adept at enlarging and can swell from a diameter of 30 to 40 μm to more than 100 μm, an increase in volume by a factor of more than 10. Starting in early adulthood, lean U.S. adults spend the next decades challenging their adipocytes by gaining on average 0.5 kg (1.1 lb) per year, with even higher weight increases among the overweight and obese,74 putting an enormous demand on the WAT depots to store triglycerides by the fifth and sixth decades of life.75
Anatomical location and genetics largely determine the proportional increase in adipocyte size and number and the physiological responses. For example, people whose subcutaneous depots maintain smaller adipocytes have fewer metabolic complications.31 Furthermore, in people who are genetically predisposed to impaired catecholamine-mediated lipolysis, white adipocytes become very large,32 a situation exacerbated by a genetic inability to recruit new adipocytes.76 As obesity progresses, preadipocyte differentiation becomes dysfunctional, leading to reduced insulin signaling, glucose uptake, and adiponectin release by the mature adipocytes.77,78 Ultimately, hypertrophic WAT growth and expansion restrict the ability of oxygen to diffuse from the capillaries into the adipocytes.77 This hypoxia constitutes a biologic red alert for the cells, altering the expression of more than 1000 genes and triggering a series of interconnected responses that ultimately lead to local resistance to both insulin and adrenergic signaling, increased inflammation, and cellular damage. Failure of the adipose tissue to continue expanding leads to overflow and subsequent deposition of triglycerides throughout the body, with ectopic accumulation in the liver and skeletal muscle. The extent of this lipotoxicity is an important determinant of the development of metabolic dysregulation, type 2 diabetes, and cardiovascular disease.79
This milieu leads to immune-system dysfunction and is thought to contribute to increased morbidity and mortality from infectious disease, currently highlighted by the worrisome epidemiologic reports about people with obesity and coronavirus disease 2019.80 Obesity is also associated with an increased risk of many types of cancer, including cancer of the breast, uterus, ovary, esophagus, stomach, colon or rectum, liver, gallbladder, pancreas, kidney, thyroid, and meninges, as well as multiple myeloma,81 but the precise mechanisms are currently unclear. Three causative agents identified so far are hyperinsulinemia, factors released during chronic inflammation, and increased estrogen production. Given the scope of disorders, the question that arises is whether excess stored triglycerides are ever benign. A metabolically healthy obese phenotype has been postulated, which has been associated with several aspects of adipocyte function, such as the release of specific adipokines.82 Whether obese persons who are metabolically healthy are nevertheless on an inexorable path toward metabolic disease remains to be determined.83
(4) Treatments for Overweight and Obesity
There are three ways to achieve a net negative energy balance: reduce food consumption, reduce nutrient absorption, and increase energy expenditure. All three ultimately converge on the common goal of reducing WAT triglyceride content. Pharmacotherapy aimed at these different pathways has been extensively reviewed.84 Several treatments currently approved by the Food and Drug Administration for the treatment of obesity directly involve adipose tissues. For example, glucagon-like peptide 1 receptor agonists such as liraglutide cause weight loss by means of appetite inhibition and are even more effective with exercise,85 yet their beneficial effects may also be mediated by stimulation of WAT lipolysis and BAT thermogenesis.86 Potential new therapies focusing on adipose tissue include bimagrumab, an inhibitor of the activin type II receptor, which reduces WAT mass while increasing the growth of skeletal muscle.87 The most effective approach to weight loss that also results in metabolic improvements is bariatric surgery.88 Although these operations reduce the complications of obesity through multiple mechanisms, much of the effectiveness is due to the profound loss of WAT mass.89 Current studies are determining the mechanisms by which weight loss is achieved, the long-term adverse effects, and the durability of the various surgical interventions.
There is also the direct approach of removing adipose tissue, but as intimated above, resecting the wrong adipose-tissue depot could worsen the metabolic effect. Noncosmetic liposuction of subcutaneous fat does not lead to long-term weight loss or improved health.90 Also, it is essential to retain at least a modicum of adipose tissue. The lipodystrophic syndromes associated with human immunodeficiency virus infection and medications used to treat it, as well as more rare genetic syndromes, have shown that too little WAT leads to lipotoxic metabolic dysfunction and leptin-deficient reproductive dysfunction.91,92 In certain circumstances, it is even beneficial to increase adipose tissue mass. Thiazolidinediones are medications that treat diabetes by activating the nuclear receptor PPAR-γ (peroxisome proliferator–activated receptor γ) and increasing the number of smaller and more insulin-responsive adipocytes that can more safely store triglycerides.93 By inducing hyperplasia instead of hypertrophy, thiazolidinediones lead to a paradoxical improvement in a patient’s metabolic profile while increasing adipocyte mass.
Could long-term BAT activation help treat obesity or related metabolic diseases? In rodents, the answer is unequivocally yes,94 but in humans, the answer has yet to be determined. As already discussed, humans have proportionally less BAT than smaller mammals, but contemporary humans may have even less BAT than is required to support their physiological and metabolic needs. BAT mass dramatically decreases with increased ambient temperatures,95 and aging also appears to induce BAT atrophy,96 raising the possibility that contemporary humans who create a thermoneutral environment are artificially lowering their BAT mass and its contribution to energy balance and metabolic health. Even the limited BAT present in adults appears to have a substantial clinical effect, because retrospective and prospective studies show an inverse association between BAT activity and BMI.97 In addition, a recent study showed that persons with BAT had healthier blood glucose, triglyceride, and high-density lipoprotein levels than persons without BAT.2 Those with BAT had a lower prevalence of cardiometabolic diseases such as type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure, and hypertension.
Clinical trials are necessary to determine the outcomes from long-term BAT activation, given that studies in rodents suggest that activating BAT could lead to compensatory food intake98 or the opposite, suppression of appetite.99 Initial prospective clinical studies have shown that long-term treatment with β3-adrenergic receptor agonists increases BAT mass and browning of WAT and is associated with improvements in insulin sensitivity and cardiometabolic risk factors.100
(5) Conclusions
The riskiest approach to human adipose tissue is to dismiss its importance. WAT lies at the heart of the obesity pandemic, and its response to excess calories has an effect on every organ system, with profound effects on morbidity and mortality worldwide. The past decade, and particularly the past 5 years, has seen an explosive growth in our understanding of adipose tissue, with work that recognizes human WAT and BAT as organs that have anatomical, functional, and genetic diversity. Going forward, fat will ideally be appreciated for what it is, a polychromatic tissue, which is as relevant and influential as other organs for sustaining human health.
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Nordic diet may improve cholesterol, blood sugar, even without weight loss
Annie Lennon | March 17, 2022
Researchers investigated the health effects of a healthy Nordic diet (HND) using metabolic analysis.
They found that the diet positively affects glucose metabolism, cholesterol, and cardiometabolic risk.
They conclude that metabolic analysis is an effective way to assess dietary outcomes.
The HND consists of berries, fish, root vegetables, and rapeseed oil (and whole-grain products and low-fat dairy). It is known to benefit various aspects of health, including weight loss, blood pressure, inflammation, and blood lipid profiles...
https://www.medicalnewstoday.com/articles/nordic-diet-may-improve-cholesterol-bl...
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Gözde Gürdenizab et al. 2022. Randomized Control Trials: Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids. Clinical Nutrition Volume 41, Issue 2, February 2022, Pages 441-451. https://doi.org/10.1016/j.clnu.2021.12.031 https://www.sciencedirect.com/science/article/pii/S0261561421005963
Annie Lennon | March 17, 2022
Researchers investigated the health effects of a healthy Nordic diet (HND) using metabolic analysis.
They found that the diet positively affects glucose metabolism, cholesterol, and cardiometabolic risk.
They conclude that metabolic analysis is an effective way to assess dietary outcomes.
The HND consists of berries, fish, root vegetables, and rapeseed oil (and whole-grain products and low-fat dairy). It is known to benefit various aspects of health, including weight loss, blood pressure, inflammation, and blood lipid profiles...
https://www.medicalnewstoday.com/articles/nordic-diet-may-improve-cholesterol-bl...
---------------------------------------------------
Gözde Gürdenizab et al. 2022. Randomized Control Trials: Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids. Clinical Nutrition Volume 41, Issue 2, February 2022, Pages 441-451. https://doi.org/10.1016/j.clnu.2021.12.031 https://www.sciencedirect.com/science/article/pii/S0261561421005963
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Keto molecule may help reverse colorectal cancer (in mice anyway!)
Annie Lennon | May 12, 2022
Researchers investigated how low carb diets reduce colorectal tumor growth in mice.
They found that a molecule produced on keto diets suppresses tumor growth and think that these results may translate over to humans.
The researchers have now initiated clinical trials to determine the molecule’s effect on human colorectal cancer...
https://www.medicalnewstoday.com/articles/keto-molecule-may-help-reverse-colorec...
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Oxana Dmitrieva-Posocco et al. 2022. β-Hydroxybutyrate suppresses colorectal cancer. Nature volume 605, pages 160–165 (2022) https://www.nature.com/articles/s41586-022-04649-6
Annie Lennon | May 12, 2022
Researchers investigated how low carb diets reduce colorectal tumor growth in mice.
They found that a molecule produced on keto diets suppresses tumor growth and think that these results may translate over to humans.
The researchers have now initiated clinical trials to determine the molecule’s effect on human colorectal cancer...
https://www.medicalnewstoday.com/articles/keto-molecule-may-help-reverse-colorec...
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Oxana Dmitrieva-Posocco et al. 2022. β-Hydroxybutyrate suppresses colorectal cancer. Nature volume 605, pages 160–165 (2022) https://www.nature.com/articles/s41586-022-04649-6
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Tirzepatide Serves Up Major Weight-Loss Win in Patients With Obesity
— SURMOUNT-1 trial tested GIP/GLP-1 receptor agonist in people without diabetes
Kristen Monaco | June 5, 2022
The combination GIP and GLP-1 receptor agonist tirzepatide (Mounjaro) could soon be the next new treatment option for people with overweight or obesity, researchers reported.
In the 72-week, phase III SURMOUNT-1 clinical trial, people with obesity, but without diabetes, on 15 mg of the once-weekly injectable had a mean percentage change in weight of -20.9% (95% CI -21.8 to -19.9%) versus -3.1% (95% CI -4.3 to -1.9) with placebo, according to Ania M. Jastreboff, MD, PhD, of the Yale University School of Medicine in New Haven, and colleagues...
...Beyond just weight loss, tirzepatide treatment resulted in improvements in waist circumference, systolic and diastolic blood pressure, fasting insulin level, and lipid levels. SF-36 physical function scores also increased more with active treatment, according to the authors.
As to be expected with a GLP-1 receptor agonist, the most common adverse events (AEs) were gastrointestinal-related: nausea, diarrhea, and constipation. There were four cases of adjudication-confirmed pancreatitis, one in each of the study arms including placebo...
...The first of its kind in this class of combination GLP-1/GIP drugs, tirzepatide was FDA approved in May for type 2 diabetes...
https://www.medpagetoday.com/meetingcoverage/ada/99060
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Ania M. Jastreboffbetal. 2022. Tirzepatide Once Weekly for the Treatment of Obesity. NEJM June 4, 2022. DOI: 10.1056/NEJMoa2206038 https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
Abstract
...Results
At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was −15.0% ... with 5-mg weekly doses of tirzepatide, −19.5% ... with 10-mg doses, and −20.9% ... with 15-mg doses and −3.1% ... with placebo .... The percentage of participants who had weight reduction of 5% or more was 85%..., 89%..., and 91% ... with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35%... with placebo; 50% ... and 57% ... of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% ... in the placebo group .... Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.
Conclusions
In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622. opens in new tab.)
— SURMOUNT-1 trial tested GIP/GLP-1 receptor agonist in people without diabetes
Kristen Monaco | June 5, 2022
The combination GIP and GLP-1 receptor agonist tirzepatide (Mounjaro) could soon be the next new treatment option for people with overweight or obesity, researchers reported.
In the 72-week, phase III SURMOUNT-1 clinical trial, people with obesity, but without diabetes, on 15 mg of the once-weekly injectable had a mean percentage change in weight of -20.9% (95% CI -21.8 to -19.9%) versus -3.1% (95% CI -4.3 to -1.9) with placebo, according to Ania M. Jastreboff, MD, PhD, of the Yale University School of Medicine in New Haven, and colleagues...
...Beyond just weight loss, tirzepatide treatment resulted in improvements in waist circumference, systolic and diastolic blood pressure, fasting insulin level, and lipid levels. SF-36 physical function scores also increased more with active treatment, according to the authors.
As to be expected with a GLP-1 receptor agonist, the most common adverse events (AEs) were gastrointestinal-related: nausea, diarrhea, and constipation. There were four cases of adjudication-confirmed pancreatitis, one in each of the study arms including placebo...
...The first of its kind in this class of combination GLP-1/GIP drugs, tirzepatide was FDA approved in May for type 2 diabetes...
https://www.medpagetoday.com/meetingcoverage/ada/99060
---------------------------------------------------------------------
Ania M. Jastreboffbetal. 2022. Tirzepatide Once Weekly for the Treatment of Obesity. NEJM June 4, 2022. DOI: 10.1056/NEJMoa2206038 https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
Abstract
...Results
At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was −15.0% ... with 5-mg weekly doses of tirzepatide, −19.5% ... with 10-mg doses, and −20.9% ... with 15-mg doses and −3.1% ... with placebo .... The percentage of participants who had weight reduction of 5% or more was 85%..., 89%..., and 91% ... with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35%... with placebo; 50% ... and 57% ... of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% ... in the placebo group .... Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.
Conclusions
In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622. opens in new tab.)
105margd
High fat diet and substances touted to improve athletic performance can activate a receptor that accelerates the progression of pre-cancerous lesions to pancreatic cancer in mice.
High fat diet, unregulated athletic exercise endurance enhancers linked to risk of pancreatic cancer
Anna Megdell | June 01, 2022
...Critical factors that promote the progression of silent pancreatic precancerous lesions to pancreatic cancer remain poorly defined, especially those that are easy to target. While most of these pre-cancerous lesions don’t develop into cancer, understanding how they progress is still crucial to finding interventions to address the rising rate of pancreatic cancer. Findings from this study indicate that people who have silent precancerous lesions, even those that are low grade, could increase their risk of developing pancreatic cancer by consuming PPARδ natural activators, like in high fat diets, or synthetic ones, like Cardarine.* Future development of effective agents to block PPARδ activation could be a new approach to prevent the progression of precancerous lesions into pancreatic cancer. Limiting exposure to high fat diets could also be considered for those with a high prevalence of pre-cancerous pancreatic lesions. But for now, the prevalent sales and use of those athletic boosting synthetic PPARδ activating substances causes the most pressing concern.
https://labblog.uofmhealth.org/lab-report/high-fat-diet-unregulated-athletic-exe...
* Cardarine is a type of chemical known as a metabolic modulator. It changes how the body uses fat. It is banned by the World Anti-Doping Agency (WADA). (WebMD)
----------------------------------------------------------------
Yi Liu et al. 2022. Rapid acceleration of KRAS-mutant pancreatic carcinogenesis via remodeling of tumor immune microenvironment by PPARδ. Nature Communications volume 13, Article number: 2665 (13 May 2022) DOI: 10.1038/s41467-022-30392-7 https://www.nature.com/articles/s41467-022-30392-7
...DISCUSSION
...activation of upregulated PPARδ (peroxisome proliferator-activated receptor-delta, a lipid nuclear receptor) in PanINs (pancreatic intraepithelial neoplasia) can strongly promote progression of asymptomatic PanIN to PDAC (pancreatic ductal adenocarcinoma).
... important potential for clinical/translational implications: PPARδ activation by intake of PPARδ ligands, whether synthetic (e.g., GW ) or natural (e.g., high levels of fatty acids in Western diets), can be potentially harmful for individuals whose pancreata harbor KRASmu (mutant pancreatic epithelial cells ) PanINs, a scenario that increases with age in humans...
...In summary, our results demonstrate the strong impact of PPARδ hyperactivation by natural or synthetic ligands in promoting the progression of KRASmu-initiated pancreatic carcinogenesis into PDAC. These findings provide a strong rationale for targeting PPARδ signaling to prevent the progression of PanIN to PDAC...
___________________________________________________
...Natural ligands for PPAR-δ include polyunsaturated fatty acids (PUFA, e.g., arachidonic and linoleic acid)) and their metabolites...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275063/
Linoleic acid is the predominant n-6 polyunsaturated fatty acid (PUFA) in the Western diet and we can obtain it from vegetable oils such as sunflower, safflower, soybean, corn, and canola oils as well as nuts and seeds.
https://www.hsph.harvard.edu/nutritionsource/2014/11/05/dietary-linoleic-acid-an...
The main charge against omega-6 fats is that the body can convert the most common one, linolenic acid, into another fatty acid called arachidonic acid, and arachidonic acid is a building block for molecules that can promote inflammation, blood clotting, and the constriction of blood vessels. But the body also converts arachidonic acid into molecules that calm inflammation and fight blood clots.
https://www.health.harvard.edu/newsletter_article/no-need-to-avoid-healthy-omega...
The major dietary sources of linoleic acid are vegetable oils, nuts, seeds, meats, and eggs. The consumption of linoleic acid in the US diet began to increase around 1969 and paralleled the introduction of soybean oil as the major commercial additive to many processed foods
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650500/
_______________________________________________
Why pancreatic cancer is on the rise
Claudia Wallis | 1 April 2022
https://www.scientificamerican.com/article/why-pancreatic-cancer-is-on-the-rise/
High fat diet, unregulated athletic exercise endurance enhancers linked to risk of pancreatic cancer
Anna Megdell | June 01, 2022
...Critical factors that promote the progression of silent pancreatic precancerous lesions to pancreatic cancer remain poorly defined, especially those that are easy to target. While most of these pre-cancerous lesions don’t develop into cancer, understanding how they progress is still crucial to finding interventions to address the rising rate of pancreatic cancer. Findings from this study indicate that people who have silent precancerous lesions, even those that are low grade, could increase their risk of developing pancreatic cancer by consuming PPARδ natural activators, like in high fat diets, or synthetic ones, like Cardarine.* Future development of effective agents to block PPARδ activation could be a new approach to prevent the progression of precancerous lesions into pancreatic cancer. Limiting exposure to high fat diets could also be considered for those with a high prevalence of pre-cancerous pancreatic lesions. But for now, the prevalent sales and use of those athletic boosting synthetic PPARδ activating substances causes the most pressing concern.
https://labblog.uofmhealth.org/lab-report/high-fat-diet-unregulated-athletic-exe...
* Cardarine is a type of chemical known as a metabolic modulator. It changes how the body uses fat. It is banned by the World Anti-Doping Agency (WADA). (WebMD)
----------------------------------------------------------------
Yi Liu et al. 2022. Rapid acceleration of KRAS-mutant pancreatic carcinogenesis via remodeling of tumor immune microenvironment by PPARδ. Nature Communications volume 13, Article number: 2665 (13 May 2022) DOI: 10.1038/s41467-022-30392-7 https://www.nature.com/articles/s41467-022-30392-7
...DISCUSSION
...activation of upregulated PPARδ (peroxisome proliferator-activated receptor-delta, a lipid nuclear receptor) in PanINs (pancreatic intraepithelial neoplasia) can strongly promote progression of asymptomatic PanIN to PDAC (pancreatic ductal adenocarcinoma).
... important potential for clinical/translational implications: PPARδ activation by intake of PPARδ ligands, whether synthetic (e.g., GW ) or natural (e.g., high levels of fatty acids in Western diets), can be potentially harmful for individuals whose pancreata harbor KRASmu (mutant pancreatic epithelial cells ) PanINs, a scenario that increases with age in humans...
...In summary, our results demonstrate the strong impact of PPARδ hyperactivation by natural or synthetic ligands in promoting the progression of KRASmu-initiated pancreatic carcinogenesis into PDAC. These findings provide a strong rationale for targeting PPARδ signaling to prevent the progression of PanIN to PDAC...
___________________________________________________
...Natural ligands for PPAR-δ include polyunsaturated fatty acids (PUFA, e.g., arachidonic and linoleic acid)) and their metabolites...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275063/
Linoleic acid is the predominant n-6 polyunsaturated fatty acid (PUFA) in the Western diet and we can obtain it from vegetable oils such as sunflower, safflower, soybean, corn, and canola oils as well as nuts and seeds.
https://www.hsph.harvard.edu/nutritionsource/2014/11/05/dietary-linoleic-acid-an...
The main charge against omega-6 fats is that the body can convert the most common one, linolenic acid, into another fatty acid called arachidonic acid, and arachidonic acid is a building block for molecules that can promote inflammation, blood clotting, and the constriction of blood vessels. But the body also converts arachidonic acid into molecules that calm inflammation and fight blood clots.
https://www.health.harvard.edu/newsletter_article/no-need-to-avoid-healthy-omega...
The major dietary sources of linoleic acid are vegetable oils, nuts, seeds, meats, and eggs. The consumption of linoleic acid in the US diet began to increase around 1969 and paralleled the introduction of soybean oil as the major commercial additive to many processed foods
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650500/
_______________________________________________
Why pancreatic cancer is on the rise
Claudia Wallis | 1 April 2022
https://www.scientificamerican.com/article/why-pancreatic-cancer-is-on-the-rise/
106margd
The U.S. diet is deadly. Here are 7 ideas to get Americans eating healthier
Allison Aubrey | August 31, 2022
1. Treat food as medicine
2. Focus on quality of calories, not just quantity
3. Expand access to dietary and lifestyle counseling
4. Support food entrepreneurs
5. Increase the number of new farmers growing healthy foods using regenerative farming techniques
6. Make school meals free for all students
7. Establish a federal 'food czar'
https://www.npr.org/sections/health-shots/2022/08/31/1120004717/the-u-s-diet-is-...
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Informing the White House Conference:
Ambitious, Actionable Recommendations to End Hunger, Advance Nutrition, and Improve Health in the United States
30 policy recommendations for a healthier country by 2030
POLICY RECOMMENDATIONS IN THIS REPORT
A. FEDERAL NUTRITION PROGRAMS
1. Increase access to and participation in federal nutrition programs by expanding eligibility,
simplifying enrollment, and improving convenience for participants.
2. Eliminate food insecurity among participants of federal nutrition programs by ensuring benefit
amounts are sufficient to meet households’ food needs.
3. Increase nutrition security by promoting dietary patterns that align with the latest
Dietary Guidelines for Americans (DGA) through federal nutrition programs.
4. Improve program convenience and benefit flexibilities for participants of Electronic Benefits
Transfer (EBT)-based programs (e.g., Supplemental Nutrition Assistance Program (SNAP) and
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)) to increase
participation in these vital programs and allow the programs to better promote food and
nutrition security.
5. Leverage the federal nutrition programs’ power in economic stimulus to support food systems
that promote foods that align with the latest DGA.
B. PUBLIC HEALTH AND NUTRITION EDUCATION
6. Strengthen, coordinate, and invest in the public health infrastructure to address nutrition,
hunger, and health.
7. Strengthen federal nutrition education programs, including the Supplemental Nutrition
Assistance Program-Education (SNAP-Ed), WIC Nutrition Education, and the Expanded Food
and Nutrition Education Program (EFNEP), to allow them to provide more effective nutrition
education to more people.
8. Improve the readability, content, and usefulness of packaged food labels to make it easier to
identify more nutritious food options both within and across food categories.
9. Reduce the marketing of foods that do not align with the latest DGA and increase the marketing
of foods that align with the latest DGA to children and populations with disproportionate rates
of diet-related chronic conditions.
10. Increase consumer understanding and improve translation of the evidence connecting food,
nutrition, and health outcomes.
11. Improve the nutritional quality of foods offered in federal, state, and local government facilities,
including worksites, military installations and facilities, national parks, and correctional facilities.
12. Create and invest in programs and policies that promote human milk feeding as the premier
source of infant nutrition.
C. HEALTH CARE
13. Accelerate access to “Food Is Medicine” services to prevent and treat diet-related illness.
14. Increase access to and insurance coverage for behavioral interventions and nutritional
counseling to improve diet and health.
15. Build a diverse health care workforce with appropriate training and expertise in diet and health.
16. Facilitate health system screening for food and nutrition insecurity and follow-up referrals to
appropriate interventions.
17. Leverage the integral role hospitals play in regional food systems and local communities to
improve food and nutrition security for community members.
D. RESEARCH AND SCIENCE
18. Create a new national nutrition science strategy to improve coordination and investment in
federal nutrition research focused on prevention and treatment of diet-related conditions.
19. Increase leadership, coordination, and investment in nutrition research at the National Institutes
of Health (NIH).
20. Utilize research and data sharing to improve nutrition policies and programs across federal
agencies.
21. Catalyze private sector and philanthropic research funding to stimulate high-integrity,
transparent investment in unbiased research that can help address the nation’s priorities for
hunger, nutrition, and health.
E. BUSINESS AND INNOVATION
22. Fund and implement a comprehensive strategy to build a national ecosystem of evidence-
based, mission-oriented business innovation to reduce hunger, improve nutrition, reduce
diet-related chronic conditions, and increase health equity.
23. Support new and small food sector businesses owned by historically underserved and
marginalized groups.
24. Encourage the private sector (food and non-food businesses) to improve food security,
nutrition, and health through food- and nutrition-focused offerings in company offices, events,
benefit packages, and insurance plan designs.
25. Increase the ability of food companies to communicate with consumers about the evidence for
healthfulness of certain food products and nutrients.
26. Improve the resiliency, accessibility, and nutritional quality of the food supply.
27. Increase the number of new small and mid-sized farmers growing specialty crops and other
foods recommended by the DGA.
28. Increase food recovery from farms, grocery stores, restaurants, and other food businesses
for the purpose of donating to entities that address hunger and food insecurity.
F. FEDERAL COORDINATION
29. Improve coordination and collaboration among, and increase accountability for, federal agencies
to address hunger, nutrition, and health.
30. Establish new structure, leadership, and authority within the federal government to increase
effectiveness and synergies of diverse hunger, nutrition, and health efforts across a
Executive Summary (7p)
https://informingwhc.org/wp-content/uploads/2022/08/Informing_White_House_Confer...
https://informingwhc.org/2022-task-force-report/
Allison Aubrey | August 31, 2022
1. Treat food as medicine
2. Focus on quality of calories, not just quantity
3. Expand access to dietary and lifestyle counseling
4. Support food entrepreneurs
5. Increase the number of new farmers growing healthy foods using regenerative farming techniques
6. Make school meals free for all students
7. Establish a federal 'food czar'
https://www.npr.org/sections/health-shots/2022/08/31/1120004717/the-u-s-diet-is-...
------------------------------------------------------------------
Informing the White House Conference:
Ambitious, Actionable Recommendations to End Hunger, Advance Nutrition, and Improve Health in the United States
30 policy recommendations for a healthier country by 2030
POLICY RECOMMENDATIONS IN THIS REPORT
A. FEDERAL NUTRITION PROGRAMS
1. Increase access to and participation in federal nutrition programs by expanding eligibility,
simplifying enrollment, and improving convenience for participants.
2. Eliminate food insecurity among participants of federal nutrition programs by ensuring benefit
amounts are sufficient to meet households’ food needs.
3. Increase nutrition security by promoting dietary patterns that align with the latest
Dietary Guidelines for Americans (DGA) through federal nutrition programs.
4. Improve program convenience and benefit flexibilities for participants of Electronic Benefits
Transfer (EBT)-based programs (e.g., Supplemental Nutrition Assistance Program (SNAP) and
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)) to increase
participation in these vital programs and allow the programs to better promote food and
nutrition security.
5. Leverage the federal nutrition programs’ power in economic stimulus to support food systems
that promote foods that align with the latest DGA.
B. PUBLIC HEALTH AND NUTRITION EDUCATION
6. Strengthen, coordinate, and invest in the public health infrastructure to address nutrition,
hunger, and health.
7. Strengthen federal nutrition education programs, including the Supplemental Nutrition
Assistance Program-Education (SNAP-Ed), WIC Nutrition Education, and the Expanded Food
and Nutrition Education Program (EFNEP), to allow them to provide more effective nutrition
education to more people.
8. Improve the readability, content, and usefulness of packaged food labels to make it easier to
identify more nutritious food options both within and across food categories.
9. Reduce the marketing of foods that do not align with the latest DGA and increase the marketing
of foods that align with the latest DGA to children and populations with disproportionate rates
of diet-related chronic conditions.
10. Increase consumer understanding and improve translation of the evidence connecting food,
nutrition, and health outcomes.
11. Improve the nutritional quality of foods offered in federal, state, and local government facilities,
including worksites, military installations and facilities, national parks, and correctional facilities.
12. Create and invest in programs and policies that promote human milk feeding as the premier
source of infant nutrition.
C. HEALTH CARE
13. Accelerate access to “Food Is Medicine” services to prevent and treat diet-related illness.
14. Increase access to and insurance coverage for behavioral interventions and nutritional
counseling to improve diet and health.
15. Build a diverse health care workforce with appropriate training and expertise in diet and health.
16. Facilitate health system screening for food and nutrition insecurity and follow-up referrals to
appropriate interventions.
17. Leverage the integral role hospitals play in regional food systems and local communities to
improve food and nutrition security for community members.
D. RESEARCH AND SCIENCE
18. Create a new national nutrition science strategy to improve coordination and investment in
federal nutrition research focused on prevention and treatment of diet-related conditions.
19. Increase leadership, coordination, and investment in nutrition research at the National Institutes
of Health (NIH).
20. Utilize research and data sharing to improve nutrition policies and programs across federal
agencies.
21. Catalyze private sector and philanthropic research funding to stimulate high-integrity,
transparent investment in unbiased research that can help address the nation’s priorities for
hunger, nutrition, and health.
E. BUSINESS AND INNOVATION
22. Fund and implement a comprehensive strategy to build a national ecosystem of evidence-
based, mission-oriented business innovation to reduce hunger, improve nutrition, reduce
diet-related chronic conditions, and increase health equity.
23. Support new and small food sector businesses owned by historically underserved and
marginalized groups.
24. Encourage the private sector (food and non-food businesses) to improve food security,
nutrition, and health through food- and nutrition-focused offerings in company offices, events,
benefit packages, and insurance plan designs.
25. Increase the ability of food companies to communicate with consumers about the evidence for
healthfulness of certain food products and nutrients.
26. Improve the resiliency, accessibility, and nutritional quality of the food supply.
27. Increase the number of new small and mid-sized farmers growing specialty crops and other
foods recommended by the DGA.
28. Increase food recovery from farms, grocery stores, restaurants, and other food businesses
for the purpose of donating to entities that address hunger and food insecurity.
F. FEDERAL COORDINATION
29. Improve coordination and collaboration among, and increase accountability for, federal agencies
to address hunger, nutrition, and health.
30. Establish new structure, leadership, and authority within the federal government to increase
effectiveness and synergies of diverse hunger, nutrition, and health efforts across a
Executive Summary (7p)
https://informingwhc.org/wp-content/uploads/2022/08/Informing_White_House_Confer...
https://informingwhc.org/2022-task-force-report/
107margd
Montserrat Rodríguez-Ayala et a. 2022. Cooking methods are associated with inflammatory factors, renal function, and other hormones and nutritional biomarkers in older adults. (Nature) Scientific Reports volume 12, Article number: 16483 (1 October 2022). https://www.nature.com/articles/s41598-022-19716-1
Abstract
...Raw, boiling, pan-frying, and toasting were associated with healthy profiles as for inflammatory markers, renal function, thyroid hormones, and serum vitamin D. On the contrary, frying and, to a less extent, stewing showed unhealthier profiles. Cooking methods not including added fats where healthier than those with added fats heated at high temperatures or during longer periods of time.
Abstract
...Raw, boiling, pan-frying, and toasting were associated with healthy profiles as for inflammatory markers, renal function, thyroid hormones, and serum vitamin D. On the contrary, frying and, to a less extent, stewing showed unhealthier profiles. Cooking methods not including added fats where healthier than those with added fats heated at high temperatures or during longer periods of time.
108kiparsky
>106 margd: 4. Support food entrepreneurs So, I work for a startup accelerator and we've seen lots of food entrepreneurs come through. Mostly, they're people who have come up with a new sort of snack, usually with some sort of health angle (cricket flour was big a few years ago, different "superfoods" and such) and of course some eco angle and all of that. Basically, they all take points 1-3 in that list as good marketing material, which in today's marketplace is really all it amounts to, at least at the scale that this white paper is working.
The typical exit for one of these companies is to be acquired by one of the major snack producers. As in tech, the startup ecosystem serves as basically free R&D for the handful of companies that you, the consumer, actually deal with. The alternative is to remain independent and compete with the major producer, who have well-established distribution channels and can easily come up with a copycat product as soon as they see you get any market traction with your new superfood-and-cricket-flour noshlets, and most people can do the math on that, so they pursue the acquisition strategy.
This does not do much to support "new and small food sector businesses owned by historically underserved and marginalized groups", of course - though it does give a nice payday to the cleverpants who came up with the new superfood-and-cricket-flour num-nums.
The problem in this case is not a lack of support for "food entrepreneurs", they're quire well provided for on the whole and they're the reason you see new snackies on the shelves at your local foodmart every month. The problem is more with the realities of the marketplace, which dictate that those tasty nibbles will always follow the same rules in the long run as the ones which preceded them: General Foods and Yum Brands et al have already more or less worked out the most profitable ways to provide consumers with foor, or at least with reasonably foodlike substances. If you want to be a food entrepreneur, which is to say, if you want to make a profit by "innovating in the food space" (yeah, people actually say stuff like that) then you're going to end up doing it their way. And unfortunately, the health of the end consumer is not a profit center for the food industry, as most of us have figured out by now.
In other words, the problem with retail food is more structural than superficial. It might be fun to imagine, as a sort of science fiction world-building exercise, a world in which a purely market-based food distribution system would manage to provide healthy food for everyone, but I'm afraid it would end up being more of a fantasy scenario than proper science fiction.
On a more hopeful note I can report that there is at least one company that I know of working seriously on point 5 on that list. Look up a company called "Indigo Ag", they're doing some interesting things within the confines of the existing market that could potentially make a difference in food production at the farm side. And since they have no retail exposure, there's actually a chance they might be able to make some headway on this.
The typical exit for one of these companies is to be acquired by one of the major snack producers. As in tech, the startup ecosystem serves as basically free R&D for the handful of companies that you, the consumer, actually deal with. The alternative is to remain independent and compete with the major producer, who have well-established distribution channels and can easily come up with a copycat product as soon as they see you get any market traction with your new superfood-and-cricket-flour noshlets, and most people can do the math on that, so they pursue the acquisition strategy.
This does not do much to support "new and small food sector businesses owned by historically underserved and marginalized groups", of course - though it does give a nice payday to the cleverpants who came up with the new superfood-and-cricket-flour num-nums.
The problem in this case is not a lack of support for "food entrepreneurs", they're quire well provided for on the whole and they're the reason you see new snackies on the shelves at your local foodmart every month. The problem is more with the realities of the marketplace, which dictate that those tasty nibbles will always follow the same rules in the long run as the ones which preceded them: General Foods and Yum Brands et al have already more or less worked out the most profitable ways to provide consumers with foor, or at least with reasonably foodlike substances. If you want to be a food entrepreneur, which is to say, if you want to make a profit by "innovating in the food space" (yeah, people actually say stuff like that) then you're going to end up doing it their way. And unfortunately, the health of the end consumer is not a profit center for the food industry, as most of us have figured out by now.
In other words, the problem with retail food is more structural than superficial. It might be fun to imagine, as a sort of science fiction world-building exercise, a world in which a purely market-based food distribution system would manage to provide healthy food for everyone, but I'm afraid it would end up being more of a fantasy scenario than proper science fiction.
On a more hopeful note I can report that there is at least one company that I know of working seriously on point 5 on that list. Look up a company called "Indigo Ag", they're doing some interesting things within the confines of the existing market that could potentially make a difference in food production at the farm side. And since they have no retail exposure, there's actually a chance they might be able to make some headway on this.
109margd
Discouraged recently to realize that we are still eating processed foods when I think I'm cooking from scratch, e.g., cream cheese in cauliflower mash, pan gravy... Only glimmer of hope is our local Costco that sells processed food that's light on chems. Not all Costco stores have similar priorities, unfortunately...
110margd
This Simple Sitting Exercise Lowers Blood Sugar and Burns Fat, Study Says
The “soleus pushup” may reduce your type 2 diabetes risk.
Jeff Csatari | October 5, 2022
...The soleus muscle is situated on the back of the lower part of your leg. This strong muscle plays a role in walking and running, according to Verywell Health, but its greatest task is keeping you from falling forward while standing. Unlike most muscles that use stored carbohydrates for fuel, the soleus doesn't rely completely on intramuscular glycogen. Instead, it uses a mixture of fuels from the blood, namely, glucose and blood fats called lipoproteins. As Hamilton puts it in a report from the University of Houston, "When activated correctly, the soleus muscle can raise local oxidative metabolism to high levels for hours, not just minutes, and does so by using a different fuel mixture."
...Here's how you can do the soleus pushup.
Sit in a chair with your feet flat on the floor and your body relaxed. Keeping the front of your foot on the floor, raise your heels to their full range of motion. Release to allow your heels to return to the floor. And repeat.
Before you start doing heel raises at your work desk, there's a caveat. "The soleus pushup looks simple from the outside, but sometimes what we see with our naked eye isn't the whole story. It's a very specific movement that right now requires wearable technology and experience to optimize the health benefits," explains Hamilton.
The researchers are working on guides to teach the proper technique without the use of specialized equipment. Meanwhile, Hamilton hopes his research will call attention to the overlooked potential of targeting small, highly oxidative muscles with contractions as a method for improving blood sugar control in a sedentary population....
https://www.eatthis.com/soleus-pushup-lower-blood-sugar-burn-fat-study/
--------------------------------------------------------------
Marc T. Hamilton et al. 2022. A potent physiological method to magnify and sustain soleus oxidative metabolism improves glucose and lipid regulation. iScience
Volume 25, Issue 9, 16 September 2022, 104869. https://www.sciencedirect.com/science/article/pii/S2589004222011415
Highlights
• We developed a method to capitalize upon the unique phenotype of the soleus
• “A high quality versus large quantity perspective” for muscle activation
• Singular movement targeting the 1 kg soleus easily sustains oxidative metabolism
• This method provides a distinct muscular activity stimulus for metabolic control
Summary
Slow oxidative muscle, most notably the soleus, is inherently well equipped with the molecular machinery for regulating blood-borne substrates. However, the entire human musculature accounts for only ∼15% of the body’s oxidative metabolism of glucose at the resting energy expenditure, despite being the body’s largest lean tissue mass. We found the human soleus muscle could raise local oxidative metabolism to high levels for hours without fatigue, during a type of soleus-dominant activity while sitting, even in unfit volunteers. Muscle biopsies revealed there was minimal glycogen use. Magnifying the otherwise negligible local energy expenditure with isolated contractions improved systemic VLDL-triglyceride and glucose homeostasis by a large magnitude, e.g., 52% less postprandial glucose excursion (∼50 mg/dL less between ∼1 and 2 h) with 60% less hyperinsulinemia. Targeting a small oxidative muscle mass (∼1% body mass) with local contractile activity is a potent method for improving systemic metabolic regulation while prolonging the benefits of oxidative metabolism.
...Method details
Soleus SPU contractions
Both experiments utilized the same type of isolated plantarflexion that was done when sitting comfortably in normal chairs. This specific type of plantarflexion depended predominantly on the soleus muscle with some assistance from the gastrocnemius muscles (Figures S3 and S4). Secondly, unlike isometric plantarflexion contractions more commonly studied, this was an isotonic soleus activation that coincided with the angular motion of the ankle only when the ankle was moving upwards (Figure S4). Thus, to not overgeneralize from this to other types of plantarflexion and for brevity, the movement is described as an SPU, or “soleus push up”...
...This singular movement by a small mass of muscle was isolated from other muscle groups typically used for large weight bearing compound movements like walking. The effects of this muscular activity were tested only while sitting comfortably. The feet were positioned on the floor and under the knees so that the knees were bent (Figure S2). The starting angle of the ankle was ∼70–90 degrees (90 degrees defined as when the tibia and sole of the foot are at a right angle). This type of plantarflexion movement was performed without adding external resistance beyond the weight of the leg (Figure S2). That avoided the necessity of using a resistance device while also minimizing potential muscle fatigue and tension-induced strain on soft tissues. Furthermore, the soleus contribution was accentuated during the seated plantarflexion because the knee was always bent, such that the metatarsophalangeal joint (MTP joint) in the foot was below the knee. The MTP joint was bending in concert with the plantarflexion of the ankle joint. When the knee is bent, the soleus contributes more to the work of plantarflexion as the gastrocnemius recruitment and energy demand is reduced compared to when the limb is straight...
{six to ten minutes?}
The “soleus pushup” may reduce your type 2 diabetes risk.
Jeff Csatari | October 5, 2022
...The soleus muscle is situated on the back of the lower part of your leg. This strong muscle plays a role in walking and running, according to Verywell Health, but its greatest task is keeping you from falling forward while standing. Unlike most muscles that use stored carbohydrates for fuel, the soleus doesn't rely completely on intramuscular glycogen. Instead, it uses a mixture of fuels from the blood, namely, glucose and blood fats called lipoproteins. As Hamilton puts it in a report from the University of Houston, "When activated correctly, the soleus muscle can raise local oxidative metabolism to high levels for hours, not just minutes, and does so by using a different fuel mixture."
...Here's how you can do the soleus pushup.
Sit in a chair with your feet flat on the floor and your body relaxed. Keeping the front of your foot on the floor, raise your heels to their full range of motion. Release to allow your heels to return to the floor. And repeat.
Before you start doing heel raises at your work desk, there's a caveat. "The soleus pushup looks simple from the outside, but sometimes what we see with our naked eye isn't the whole story. It's a very specific movement that right now requires wearable technology and experience to optimize the health benefits," explains Hamilton.
The researchers are working on guides to teach the proper technique without the use of specialized equipment. Meanwhile, Hamilton hopes his research will call attention to the overlooked potential of targeting small, highly oxidative muscles with contractions as a method for improving blood sugar control in a sedentary population....
https://www.eatthis.com/soleus-pushup-lower-blood-sugar-burn-fat-study/
--------------------------------------------------------------
Marc T. Hamilton et al. 2022. A potent physiological method to magnify and sustain soleus oxidative metabolism improves glucose and lipid regulation. iScience
Volume 25, Issue 9, 16 September 2022, 104869. https://www.sciencedirect.com/science/article/pii/S2589004222011415
Highlights
• We developed a method to capitalize upon the unique phenotype of the soleus
• “A high quality versus large quantity perspective” for muscle activation
• Singular movement targeting the 1 kg soleus easily sustains oxidative metabolism
• This method provides a distinct muscular activity stimulus for metabolic control
Summary
Slow oxidative muscle, most notably the soleus, is inherently well equipped with the molecular machinery for regulating blood-borne substrates. However, the entire human musculature accounts for only ∼15% of the body’s oxidative metabolism of glucose at the resting energy expenditure, despite being the body’s largest lean tissue mass. We found the human soleus muscle could raise local oxidative metabolism to high levels for hours without fatigue, during a type of soleus-dominant activity while sitting, even in unfit volunteers. Muscle biopsies revealed there was minimal glycogen use. Magnifying the otherwise negligible local energy expenditure with isolated contractions improved systemic VLDL-triglyceride and glucose homeostasis by a large magnitude, e.g., 52% less postprandial glucose excursion (∼50 mg/dL less between ∼1 and 2 h) with 60% less hyperinsulinemia. Targeting a small oxidative muscle mass (∼1% body mass) with local contractile activity is a potent method for improving systemic metabolic regulation while prolonging the benefits of oxidative metabolism.
...Method details
Soleus SPU contractions
Both experiments utilized the same type of isolated plantarflexion that was done when sitting comfortably in normal chairs. This specific type of plantarflexion depended predominantly on the soleus muscle with some assistance from the gastrocnemius muscles (Figures S3 and S4). Secondly, unlike isometric plantarflexion contractions more commonly studied, this was an isotonic soleus activation that coincided with the angular motion of the ankle only when the ankle was moving upwards (Figure S4). Thus, to not overgeneralize from this to other types of plantarflexion and for brevity, the movement is described as an SPU, or “soleus push up”...
...This singular movement by a small mass of muscle was isolated from other muscle groups typically used for large weight bearing compound movements like walking. The effects of this muscular activity were tested only while sitting comfortably. The feet were positioned on the floor and under the knees so that the knees were bent (Figure S2). The starting angle of the ankle was ∼70–90 degrees (90 degrees defined as when the tibia and sole of the foot are at a right angle). This type of plantarflexion movement was performed without adding external resistance beyond the weight of the leg (Figure S2). That avoided the necessity of using a resistance device while also minimizing potential muscle fatigue and tension-induced strain on soft tissues. Furthermore, the soleus contribution was accentuated during the seated plantarflexion because the knee was always bent, such that the metatarsophalangeal joint (MTP joint) in the foot was below the knee. The MTP joint was bending in concert with the plantarflexion of the ankle joint. When the knee is bent, the soleus contributes more to the work of plantarflexion as the gastrocnemius recruitment and energy demand is reduced compared to when the limb is straight...
{six to ten minutes?}
111margd
...maternal ultra-processed food consumption during child rearing might have a stronger association with offspring overweight or obesity than peripregnancy ultra-processed food consumption...
...ultra-processed foods (categorized) into nine subgroups: ultra-processed breads and breakfast foods; sauces, cheeses, spreads and gravies; beverages; packaged sweets and desserts; dairy based desserts; frozen and ready-to-eat meals; packaged savory snacks; meats and meat substitute products; others (eg, liquor, non-dairy creamers)...
...ultra-processed breads and breakfast foods {consumed by child?} were independently associated with childhood risk of overweight or obesity...
...Peripregnancy consumption of...sugar sweetened beverages (relative risk per one standard deviation increase 1.08...) and dairy based desserts (1.08...) were more strongly associated (than other ultra-processed foods} with the risk of overweight or obesity in offspring...
Yiqing Wang et al. 2022. Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: results from three prospective cohort studies. BMJ 2022;379:e071767 (Published 05 October 2022) doi: https://doi.org/10.1136/bmj-2022-071767 https://www.bmj.com/content/379/bmj-2022-071767
Abstract
...Results
...maternal consumption of ultra-processed foods during the child rearing period was associated with overweight or obesity in offspring, with a 26% higher risk in the group with the highest maternal ultra-processed food consumption (group 5) versus the lowest consumption group (group 1; relative risk 1.2...) {N=19 958}.
...while rates were higher, peripregnancy ultra-processed food intake was not significantly associated with an increased risk of offspring overweight or obesity (relative risk 1.17...). {N=2925}
Conclusions
...These data support the importance of refining dietary recommendations and the development of programs to improve nutrition for women of reproductive age to promote offspring health.
.
.
.
Discussion
In this large cohort study of mothers and children with long term follow-up, we found that maternal consumption of ultra-processed foods during the child rearing period was associated with an increased risk of developing overweight or obesity in offspring during childhood and adolescence, independent of offspring’s intake of ultra-processed foods, physical activity, and sedentary time. Offspring of mothers who were in the highest consumption group of ultra-processed food had a 26% increased risk of incident overweight or obesity compared with mothers in the lowest consumption group. These associations were similar among participants with different risk profiles, including maternal body weight, history of pregnancy complications, gestational weight gain, offspring sex, birth weight, and gestational age. In a subsample of mother-child pairs, the positive association between maternal ultra-processed food consumption during child rearing and offspring overweight or obesity remained even after adjusting for peripregnancy ultra-processed food consumption, suggesting that maternal ultra-processed food consumption during child rearing might have a stronger association with offspring overweight or obesity than peripregnancy ultra-processed food consumption.
...Potential mechanisms
Although the underlying pathways of our findings have not yet been fully elucidated and remain beyond the scope of this investigation, maternal diet during child rearing is likely to shape offspring’s diet and lifestyle choices, which subsequently exert a profound impact on their risk of overweight or obesity.4748 Randomized controlled trials have previously shown that parent-only interventions are similarly effective compared with parent-child interventions on child weight loss... The positive correlation between maternal and offspring consumption of ultra-processed foods in our cohort supports these hypotheses. Our results showed that the association between maternal ultra-processed food intake during the child rearing period and offspring risk of overweight or obesity was independent of offspring’s lifestyle risk factors. This finding indicates that there might be other pathways through which maternal ultra-processed food intake might influence childhood overweight risk; for example, long term in utero imprinting and the presence of uncharacterized gene by environment factors... Further research is needed to investigate these pathways.
There are a few potential mechanisms by which peripregnancy ultra-processed food intake could affect offspring adiposity, including epigenetic modification of offspring’s susceptibility to obesity. Animal and human studies have shown that maternal undernutrition and poor diet quality could lead to persistent epigenetic change in genes involved in the regulation of growth, energy balance, and insulin resistance in offspring...Other biological mechanisms might involve the proinflammatory additives in ultra-processed foods, including sodium,... emulsifiers,... sugar,... and artificial sweeteners.... Chronic maternal inflammation, possibly mediated through ultra-processed food intake, has been linked to increased offspring adiposity in mice and humans.... For example, using an experimental model for human gut microbial communities, Chassaing and colleagues showed that synthetic emulsifiers polysorbate 80 and carboxymethylcellulose increased the proinflammatory potential of human gut bacteria... Emulsifiers and sweeteners are common ingredients found in store bought beverages and dairy based desserts such as ice cream and frozen yogurt, both of which were associated with childhood overweight or obesity in our peripregnancy analysis. However, larger studies with dietary assessment specifically targeting the pregnancy period are needed to confirm our findings.
Conclusion and public health implications
We found that maternal consumption of ultra-processed foods was associated with an increased risk of incident overweight or obesity in offspring, independent of various maternal and offspring factors. Our study highlights the potential benefits of limiting ultra-processed food consumption among mothers and women of reproductive age to reduce the risk of overweight in their children. However, we should not overlook social determinants of health that could impede women from reducing ultra-processed food intake. These might include a lack of adequate time to prepare unprocessed food, the additional costs of a more healthy diet (including limited shelf life that might result in greater waste), the possibility that mothers are not solely responsible for household foods, and limited access to healthy food options due to geographical location.... Additionally, many women might already experience shame for weight related health behaviors during pregnancy and child rearing,... and we caution against using these data to further stigmatize their food choices.
Addressing these financial and social structural barriers to making healthy food choices is critical for developing achievable and responsible dietary guidelines for women of child bearing age. Further studies are warranted to investigate specific biological mechanisms and socioeconomic determinants underlying the observed associations between maternal ultra-processed food intake and offspring overweight and obesity.
...ultra-processed foods (categorized) into nine subgroups: ultra-processed breads and breakfast foods; sauces, cheeses, spreads and gravies; beverages; packaged sweets and desserts; dairy based desserts; frozen and ready-to-eat meals; packaged savory snacks; meats and meat substitute products; others (eg, liquor, non-dairy creamers)...
...ultra-processed breads and breakfast foods {consumed by child?} were independently associated with childhood risk of overweight or obesity...
...Peripregnancy consumption of...sugar sweetened beverages (relative risk per one standard deviation increase 1.08...) and dairy based desserts (1.08...) were more strongly associated (than other ultra-processed foods} with the risk of overweight or obesity in offspring...
Yiqing Wang et al. 2022. Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: results from three prospective cohort studies. BMJ 2022;379:e071767 (Published 05 October 2022) doi: https://doi.org/10.1136/bmj-2022-071767 https://www.bmj.com/content/379/bmj-2022-071767
Abstract
...Results
...maternal consumption of ultra-processed foods during the child rearing period was associated with overweight or obesity in offspring, with a 26% higher risk in the group with the highest maternal ultra-processed food consumption (group 5) versus the lowest consumption group (group 1; relative risk 1.2...) {N=19 958}.
...while rates were higher, peripregnancy ultra-processed food intake was not significantly associated with an increased risk of offspring overweight or obesity (relative risk 1.17...). {N=2925}
Conclusions
...These data support the importance of refining dietary recommendations and the development of programs to improve nutrition for women of reproductive age to promote offspring health.
.
.
.
Discussion
In this large cohort study of mothers and children with long term follow-up, we found that maternal consumption of ultra-processed foods during the child rearing period was associated with an increased risk of developing overweight or obesity in offspring during childhood and adolescence, independent of offspring’s intake of ultra-processed foods, physical activity, and sedentary time. Offspring of mothers who were in the highest consumption group of ultra-processed food had a 26% increased risk of incident overweight or obesity compared with mothers in the lowest consumption group. These associations were similar among participants with different risk profiles, including maternal body weight, history of pregnancy complications, gestational weight gain, offspring sex, birth weight, and gestational age. In a subsample of mother-child pairs, the positive association between maternal ultra-processed food consumption during child rearing and offspring overweight or obesity remained even after adjusting for peripregnancy ultra-processed food consumption, suggesting that maternal ultra-processed food consumption during child rearing might have a stronger association with offspring overweight or obesity than peripregnancy ultra-processed food consumption.
...Potential mechanisms
Although the underlying pathways of our findings have not yet been fully elucidated and remain beyond the scope of this investigation, maternal diet during child rearing is likely to shape offspring’s diet and lifestyle choices, which subsequently exert a profound impact on their risk of overweight or obesity.4748 Randomized controlled trials have previously shown that parent-only interventions are similarly effective compared with parent-child interventions on child weight loss... The positive correlation between maternal and offspring consumption of ultra-processed foods in our cohort supports these hypotheses. Our results showed that the association between maternal ultra-processed food intake during the child rearing period and offspring risk of overweight or obesity was independent of offspring’s lifestyle risk factors. This finding indicates that there might be other pathways through which maternal ultra-processed food intake might influence childhood overweight risk; for example, long term in utero imprinting and the presence of uncharacterized gene by environment factors... Further research is needed to investigate these pathways.
There are a few potential mechanisms by which peripregnancy ultra-processed food intake could affect offspring adiposity, including epigenetic modification of offspring’s susceptibility to obesity. Animal and human studies have shown that maternal undernutrition and poor diet quality could lead to persistent epigenetic change in genes involved in the regulation of growth, energy balance, and insulin resistance in offspring...Other biological mechanisms might involve the proinflammatory additives in ultra-processed foods, including sodium,... emulsifiers,... sugar,... and artificial sweeteners.... Chronic maternal inflammation, possibly mediated through ultra-processed food intake, has been linked to increased offspring adiposity in mice and humans.... For example, using an experimental model for human gut microbial communities, Chassaing and colleagues showed that synthetic emulsifiers polysorbate 80 and carboxymethylcellulose increased the proinflammatory potential of human gut bacteria... Emulsifiers and sweeteners are common ingredients found in store bought beverages and dairy based desserts such as ice cream and frozen yogurt, both of which were associated with childhood overweight or obesity in our peripregnancy analysis. However, larger studies with dietary assessment specifically targeting the pregnancy period are needed to confirm our findings.
Conclusion and public health implications
We found that maternal consumption of ultra-processed foods was associated with an increased risk of incident overweight or obesity in offspring, independent of various maternal and offspring factors. Our study highlights the potential benefits of limiting ultra-processed food consumption among mothers and women of reproductive age to reduce the risk of overweight in their children. However, we should not overlook social determinants of health that could impede women from reducing ultra-processed food intake. These might include a lack of adequate time to prepare unprocessed food, the additional costs of a more healthy diet (including limited shelf life that might result in greater waste), the possibility that mothers are not solely responsible for household foods, and limited access to healthy food options due to geographical location.... Additionally, many women might already experience shame for weight related health behaviors during pregnancy and child rearing,... and we caution against using these data to further stigmatize their food choices.
Addressing these financial and social structural barriers to making healthy food choices is critical for developing achievable and responsible dietary guidelines for women of child bearing age. Further studies are warranted to investigate specific biological mechanisms and socioeconomic determinants underlying the observed associations between maternal ultra-processed food intake and offspring overweight and obesity.
112margd
Low-Carb Diet Helps Cut HbA1c in Prediabetes
— Could be a useful approach for preventing, treating type 2 diabetes, says researcher
Kristen Monaco | October 26, 2022
https://www.medpagetoday.com/primarycare/dietnutrition/101428
--------------------------------------------------------
Kirsten S. Dorans et al. 2022. Effects of a Low-Carbohydrate Dietary Intervention on Hemoglobin A1cA Randomized Clinical Trial. JAMA Netw Open. 26 Oct 2022;5(10):e2238645. doi:10.1001/jamanetworkopen.2022.38645 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797714
Key Points
Question What is the effect of a dietary intervention promoting a low-carbohydrate diet compared with usual diet on 6-month change in hemoglobin A1c among adults with untreated hemoglobin A1c of 6.0% to 6.9%?
Findings In this randomized clinical trial that included 150 adults, the low-carbohydrate diet intervention significantly reduced hemoglobin A1c by 0.23% compared with usual diet over 6 months.
Meaning These findings suggest that a low-carbohydrate diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed.
___________________________________________
{"if sustained"...}
— Could be a useful approach for preventing, treating type 2 diabetes, says researcher
Kristen Monaco | October 26, 2022
https://www.medpagetoday.com/primarycare/dietnutrition/101428
--------------------------------------------------------
Kirsten S. Dorans et al. 2022. Effects of a Low-Carbohydrate Dietary Intervention on Hemoglobin A1cA Randomized Clinical Trial. JAMA Netw Open. 26 Oct 2022;5(10):e2238645. doi:10.1001/jamanetworkopen.2022.38645 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797714
Key Points
Question What is the effect of a dietary intervention promoting a low-carbohydrate diet compared with usual diet on 6-month change in hemoglobin A1c among adults with untreated hemoglobin A1c of 6.0% to 6.9%?
Findings In this randomized clinical trial that included 150 adults, the low-carbohydrate diet intervention significantly reduced hemoglobin A1c by 0.23% compared with usual diet over 6 months.
Meaning These findings suggest that a low-carbohydrate diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed.
___________________________________________
{"if sustained"...}
113margd
A New Way To Lose Weight Could Change Your Metabolism
São Paulo Research Foundation November 11, 2022
...According to a study comparing the effects of protein and calorie restriction diets in humans, reducing protein consumption may help control metabolic syndrome and some of its primary symptoms, such as obesity, diabetes, and high blood pressure (hypertension).
...“The study showed that cutting protein intake to 0.8 g per kg of body weight was sufficient to achieve almost the same clinical results as restricting calories, but without the need to reduce calorie intake. The results suggest that protein restriction may be one of the key factors leading to the known benefits of dietary restriction. Protein restriction dieting may therefore be a more attractive nutritional strategy and easier to follow for people with metabolic syndrome,” said Rafael Ferraz-Bannitz, first author of the article and currently a postdoctoral researcher at the Joslin Diabetes Center in Harvard Medical School in the United States.
...A conventional Western diet of 50% carbohydrates, 20% protein, and 30% fat was served to one group, but it contained 25% fewer calories...Protein consumption was lowered to 10% in the second group. Each volunteer’s calorie intake was matched to their baseline energy expenditure. 4 grams of salt were consumed daily by both groups.
...The results showed that both the calorie and protein restriction groups lost weight owing to a decrease in body fat and that the symptoms of metabolic syndrome improved. Decreased body fat is known to be associated with reduced blood sugar and more normal levels of lipids and blood pressure.
...The results showed that (after 27 days) both the calorie and protein restriction groups lost weight owing to a decrease in body fat and that the symptoms of metabolic syndrome improved. Decreased body fat is known to be associated with reduced blood sugar and more normal levels of lipids and blood pressure...
https://scitechdaily.com/a-new-way-to-lose-weight-could-change-your-metabolism/
---------------------------------------------
Rebeca A. Beraldo et al. 2022. Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial. 28 June 2022, Nutrients.
DOI: 10.3390/nu14132670
...5. Conclusions
In conclusion, we found that PR {protein restriction mimicked CR {calorie restriction} in regard to the amelioration of symptoms of metabolic syndrome, suggesting that protein is a primary driver underlying the beneficial effects of food restriction. Our data suggest that PR may be a relatively simple dietary intervention to help control glycemia, lipid levels, body weight, and blood pressure in individuals with metabolic syndrome.
São Paulo Research Foundation November 11, 2022
...According to a study comparing the effects of protein and calorie restriction diets in humans, reducing protein consumption may help control metabolic syndrome and some of its primary symptoms, such as obesity, diabetes, and high blood pressure (hypertension).
...“The study showed that cutting protein intake to 0.8 g per kg of body weight was sufficient to achieve almost the same clinical results as restricting calories, but without the need to reduce calorie intake. The results suggest that protein restriction may be one of the key factors leading to the known benefits of dietary restriction. Protein restriction dieting may therefore be a more attractive nutritional strategy and easier to follow for people with metabolic syndrome,” said Rafael Ferraz-Bannitz, first author of the article and currently a postdoctoral researcher at the Joslin Diabetes Center in Harvard Medical School in the United States.
...A conventional Western diet of 50% carbohydrates, 20% protein, and 30% fat was served to one group, but it contained 25% fewer calories...Protein consumption was lowered to 10% in the second group. Each volunteer’s calorie intake was matched to their baseline energy expenditure. 4 grams of salt were consumed daily by both groups.
...The results showed that both the calorie and protein restriction groups lost weight owing to a decrease in body fat and that the symptoms of metabolic syndrome improved. Decreased body fat is known to be associated with reduced blood sugar and more normal levels of lipids and blood pressure.
...The results showed that (after 27 days) both the calorie and protein restriction groups lost weight owing to a decrease in body fat and that the symptoms of metabolic syndrome improved. Decreased body fat is known to be associated with reduced blood sugar and more normal levels of lipids and blood pressure...
https://scitechdaily.com/a-new-way-to-lose-weight-could-change-your-metabolism/
---------------------------------------------
Rebeca A. Beraldo et al. 2022. Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial. 28 June 2022, Nutrients.
DOI: 10.3390/nu14132670
...5. Conclusions
In conclusion, we found that PR {protein restriction mimicked CR {calorie restriction} in regard to the amelioration of symptoms of metabolic syndrome, suggesting that protein is a primary driver underlying the beneficial effects of food restriction. Our data suggest that PR may be a relatively simple dietary intervention to help control glycemia, lipid levels, body weight, and blood pressure in individuals with metabolic syndrome.
1142wonderY
>113 margd: I just watched the documentary Forks Over Knives, and this seems to be part of their argument. I’m going to take a look at the companion book.
115margd
>114 2wonderY: After a certain age, Japanese people tend to eat rice and vegetables?
116margd
OT: cognitive benefits of kale, beans, tea, spinach, broccoli, tomatoes and tomato sauce, apples, wine, oranges, pears, olive oil. Some more than others, but all beneficial in total intake.
Antioxidant Flavonols Linked to Slower Memory Decline
American Academy of Neurology | November 22, 2022
Summary: Increasing consumption of food and drinks high in antioxidant flavonols helps slow memory and cognitive decline, a new study reports.
People who eat or drink more foods with antioxidant flavonols, which are found in several fruits and vegetables as well as tea and wine, may have a slower rate of memory decline, according to a study published in the November 22, 2022, online issue of Neurology.
...The study also broke the flavonol class down into the four constituents: kaempferol, quercetin, myricetin and isorhamnetin.
The top food contributors for each category were: kale, beans, tea, spinach and broccoli for kaempferol; tomatoes, kale, apples and tea for quercetin; tea, wine, kale, oranges and tomatoes for myricetin; and pears, olive oil, wine and tomato sauce for isorhamnetin.
People who had the highest intake of kaempferol had a 0.4 units per decade slower rate of cognitive decline compared to those in the lowest group. Those with the highest intake of quercetin had a 0.2 units per decade slower rate of cognitive decline compared to those in the lowest group. And people with the highest intake of myricetin had a 0.3 units per decade slower rate of cognitive decline compared to those in the lowest group. Dietary isorhamnetin was not tied to global cognition...
https://neurosciencenews.com/flavonols-memory-decline-21922/
---------------------------------------------
Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities
Thomas Monroe Holland, Puja Agarwal, Yamin Wang, Klodian Dhana, Sue E. Leurgans, Kyla Shea, Sarah L Booth, Kumar Rajan, Julie A. Schneider, Lisa L. Barnes
Neurology Nov 2022, 10.1212/WNL.0000000000201541; DOI: 10.1212/WNL.0000000000201541 https://n.neurology.org/content/early/2022/11/22/WNL.0000000000201541
Antioxidant Flavonols Linked to Slower Memory Decline
American Academy of Neurology | November 22, 2022
Summary: Increasing consumption of food and drinks high in antioxidant flavonols helps slow memory and cognitive decline, a new study reports.
People who eat or drink more foods with antioxidant flavonols, which are found in several fruits and vegetables as well as tea and wine, may have a slower rate of memory decline, according to a study published in the November 22, 2022, online issue of Neurology.
...The study also broke the flavonol class down into the four constituents: kaempferol, quercetin, myricetin and isorhamnetin.
The top food contributors for each category were: kale, beans, tea, spinach and broccoli for kaempferol; tomatoes, kale, apples and tea for quercetin; tea, wine, kale, oranges and tomatoes for myricetin; and pears, olive oil, wine and tomato sauce for isorhamnetin.
People who had the highest intake of kaempferol had a 0.4 units per decade slower rate of cognitive decline compared to those in the lowest group. Those with the highest intake of quercetin had a 0.2 units per decade slower rate of cognitive decline compared to those in the lowest group. And people with the highest intake of myricetin had a 0.3 units per decade slower rate of cognitive decline compared to those in the lowest group. Dietary isorhamnetin was not tied to global cognition...
https://neurosciencenews.com/flavonols-memory-decline-21922/
---------------------------------------------
Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities
Thomas Monroe Holland, Puja Agarwal, Yamin Wang, Klodian Dhana, Sue E. Leurgans, Kyla Shea, Sarah L Booth, Kumar Rajan, Julie A. Schneider, Lisa L. Barnes
Neurology Nov 2022, 10.1212/WNL.0000000000201541; DOI: 10.1212/WNL.0000000000201541 https://n.neurology.org/content/early/2022/11/22/WNL.0000000000201541
1172wonderY
The soleus pushup is being studied as a unique way the body processes glucose in the bloodstream.
https://scitechdaily.com/groundbreaking-discovery-of-special-muscle-that-can-pro...
https://scitechdaily.com/groundbreaking-discovery-of-special-muscle-that-can-pro...
118margd
Interesting--I'll see if I can find previous post to link, but earlier, Chinese scientists were able to reverse Type 2 diabetes with a fiber-heavy diet. Now it seems intermittent fasting can also result in remission:
Intermittent Fasting Can Lead to Type 2 Diabetes Remission
Marlene Busko | December 14, 2022
In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.
Importantly, "this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage" type 2 diabetes, the authors report.
Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which "suggests the possibility of remission for patients with longer duration" of diabetes, they note.
In addition, antidiabetic medication costs decreased by 77% compared to baseline, in patients in the intermittent-fasting intervention group...
This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).
After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%) compared with only 2.8% of the 36 patients in the control group.
At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%)...
On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months...
This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.
Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity)...
On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage* and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.
On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50% to 65% of total energy intake from carbohydrates, 15% to 20% from protein, and 20% to 30% from fat, and 5 g or more fiber per serving.
Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.
https://scitechdaily.com/intermittent-fasting-completely-reverses-type-2-diabete...
* Solid beverages are manufactured from raw materials such as fruit juice, plant extracts and sugar, and have a water content of less than 5%. The dried raw materials are ground into fine powder and then mixed with formula products, or are directly spray dried into powder. https://www.transparencymarketresearch.com/solid-beverage-market.html
-----------------------------------------------
Xiao Yang et al. 2022. Effect of an Intermittent Calorie-restricted Diet on Type 2 Diabetes Remission: A Randomized Controlled Trial. The Journal of Clinical Endocrinology & Metabolism, dgac661, https://doi.org/10.1210/clinem/dgac661 Published: 14 December 2022 (Corrected proof) https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgac66...
Abstract
...Methods
Participants between ages 38 and 72 years with a duration of T2D of 1 to 11 years, a body mass index (BMI) of 19.1 to 30.4, 66.7% male, and antidiabetic agent use and/or insulin injection were randomly allocated at a ratio of 1:1 to the Chinese Medical Nutrition Therapy (CMNT) or control group. The primary outcome was diabetes remission, defined as a stable glycated hemoglobin A1c (HbA1c) level of less than 48 mmol/mol (less than 6.5%) for at least 3 months after discontinuing all antidiabetic medications. The secondary outcomes included HbA1c level, fasting blood glucose level, blood pressure, weight, quality of life, and medication costs. We conducted a 12-month follow-up to assess the continuation of remission.
Results
On completing the 3-month intervention plus 3-month follow-up, 47.2% (17/36) of participants achieved diabetes remission in the CMNT group, whereas only 2.8% (1/36) of individuals achieved remission in the control group (odds ratio 31.32...). The mean body weight of participants in the CMNT group was reduced by 5.93 kg...compared to 0.27 kg...in the control group. After the 12-month follow-up, 44.4% (16/36) of the participants achieved sustained remission, with an HbA1c level of 6.33%... The medication costs of the CMNT group were 77.22% lower than those of the control group (60.4/month vs 265.1/month).
Conclusion
This study demonstrated the clinical efficacy of CMNT in achieving diabetes remission for at least 1 year.
Intermittent Fasting Can Lead to Type 2 Diabetes Remission
Marlene Busko | December 14, 2022
In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.
Importantly, "this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage" type 2 diabetes, the authors report.
Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which "suggests the possibility of remission for patients with longer duration" of diabetes, they note.
In addition, antidiabetic medication costs decreased by 77% compared to baseline, in patients in the intermittent-fasting intervention group...
This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).
After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%) compared with only 2.8% of the 36 patients in the control group.
At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%)...
On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months...
This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.
Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity)...
On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage* and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.
On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50% to 65% of total energy intake from carbohydrates, 15% to 20% from protein, and 20% to 30% from fat, and 5 g or more fiber per serving.
Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.
https://scitechdaily.com/intermittent-fasting-completely-reverses-type-2-diabete...
* Solid beverages are manufactured from raw materials such as fruit juice, plant extracts and sugar, and have a water content of less than 5%. The dried raw materials are ground into fine powder and then mixed with formula products, or are directly spray dried into powder. https://www.transparencymarketresearch.com/solid-beverage-market.html
-----------------------------------------------
Xiao Yang et al. 2022. Effect of an Intermittent Calorie-restricted Diet on Type 2 Diabetes Remission: A Randomized Controlled Trial. The Journal of Clinical Endocrinology & Metabolism, dgac661, https://doi.org/10.1210/clinem/dgac661 Published: 14 December 2022 (Corrected proof) https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgac66...
Abstract
...Methods
Participants between ages 38 and 72 years with a duration of T2D of 1 to 11 years, a body mass index (BMI) of 19.1 to 30.4, 66.7% male, and antidiabetic agent use and/or insulin injection were randomly allocated at a ratio of 1:1 to the Chinese Medical Nutrition Therapy (CMNT) or control group. The primary outcome was diabetes remission, defined as a stable glycated hemoglobin A1c (HbA1c) level of less than 48 mmol/mol (less than 6.5%) for at least 3 months after discontinuing all antidiabetic medications. The secondary outcomes included HbA1c level, fasting blood glucose level, blood pressure, weight, quality of life, and medication costs. We conducted a 12-month follow-up to assess the continuation of remission.
Results
On completing the 3-month intervention plus 3-month follow-up, 47.2% (17/36) of participants achieved diabetes remission in the CMNT group, whereas only 2.8% (1/36) of individuals achieved remission in the control group (odds ratio 31.32...). The mean body weight of participants in the CMNT group was reduced by 5.93 kg...compared to 0.27 kg...in the control group. After the 12-month follow-up, 44.4% (16/36) of the participants achieved sustained remission, with an HbA1c level of 6.33%... The medication costs of the CMNT group were 77.22% lower than those of the control group (60.4/month vs 265.1/month).
Conclusion
This study demonstrated the clinical efficacy of CMNT in achieving diabetes remission for at least 1 year.
119margd
>95 margd: contd.
Low levels of vitamin D in the brain linked to increased dementia risk
Robby Berman | December 8, 2022
For the first time, a new study explored vitamin D levels in the human brain and the potential effect on cognitive outcomes.
Researchers found that higher levels of vitamin D are associated with a lower risk of dementia in older adults.
Despite the findings, the exact role of vitamin D in cognitive function is not yet fully understood.
...The study found that better cognitive function is associated with people who have higher concentrations of vitamin D in their brains. Before the study, it had been unclear whether vitamin D was present in the brain at all.
...The researchers found that higher brain vitamin D concentrations in all four brain areas were associated with a 25% to 33% lower chance of developing dementia or mild cognitive impairment by the time of individuals’ last visit before death.
...the study found no correlation between vitamin D levels and amyloid plaques, which were previously thought to be among the potential causes of AD
...researchers observed no sign of an association with Lewy bodies, suggesting that vitamin D is not linked to Lewy body dementia. They also did not find a link between vitamin D, white matter lesions, or signs of mini-stroke.
...(Lead author Kyla Shea, Ph.D., a researcher at Tufts University in Massachusetts specializing in the role of micronutrients in age-related disease and disability) noted that it seems vitamin D is involved in cell-signaling pathways that may be part of neurodegeneration...
https://www.medicalnewstoday.com/articles/dementia-risk-low-levels-vitamin-d-lin...
-----------------------------------------------------
M Kyla Shea et al. 2022. Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults. Alzheimer's & Dementia. First published: 07 December 2022. htt ps://doi.org/10.1002/alz.12836 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12836
Abstract
...Results The main form of vitamin D in all brain regions measured was 25(OH)D3. Higher brain 25(OH)D3 concentrations were associated with a 25% to 33% lower odds of dementia or mild cognitive impairment (MCI) at the last visit before death (all P .031 or less). However, brain 25(OH)D concentrations were not associated with any post-mortem neuropathology outcome studied.
Discussion Higher brain 25(OH)D3 concentrations were associated with better cognitive function prior to death. Additional research is needed to clarify the specific mechanisms underlying this potentially protective relationship.
Low levels of vitamin D in the brain linked to increased dementia risk
Robby Berman | December 8, 2022
For the first time, a new study explored vitamin D levels in the human brain and the potential effect on cognitive outcomes.
Researchers found that higher levels of vitamin D are associated with a lower risk of dementia in older adults.
Despite the findings, the exact role of vitamin D in cognitive function is not yet fully understood.
...The study found that better cognitive function is associated with people who have higher concentrations of vitamin D in their brains. Before the study, it had been unclear whether vitamin D was present in the brain at all.
...The researchers found that higher brain vitamin D concentrations in all four brain areas were associated with a 25% to 33% lower chance of developing dementia or mild cognitive impairment by the time of individuals’ last visit before death.
...the study found no correlation between vitamin D levels and amyloid plaques, which were previously thought to be among the potential causes of AD
...researchers observed no sign of an association with Lewy bodies, suggesting that vitamin D is not linked to Lewy body dementia. They also did not find a link between vitamin D, white matter lesions, or signs of mini-stroke.
...(Lead author Kyla Shea, Ph.D., a researcher at Tufts University in Massachusetts specializing in the role of micronutrients in age-related disease and disability) noted that it seems vitamin D is involved in cell-signaling pathways that may be part of neurodegeneration...
https://www.medicalnewstoday.com/articles/dementia-risk-low-levels-vitamin-d-lin...
-----------------------------------------------------
M Kyla Shea et al. 2022. Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults. Alzheimer's & Dementia. First published: 07 December 2022. htt ps://doi.org/10.1002/alz.12836 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12836
Abstract
...Results The main form of vitamin D in all brain regions measured was 25(OH)D3. Higher brain 25(OH)D3 concentrations were associated with a 25% to 33% lower odds of dementia or mild cognitive impairment (MCI) at the last visit before death (all P .031 or less). However, brain 25(OH)D concentrations were not associated with any post-mortem neuropathology outcome studied.
Discussion Higher brain 25(OH)D3 concentrations were associated with better cognitive function prior to death. Additional research is needed to clarify the specific mechanisms underlying this potentially protective relationship.
120margd
>119 margd: contd. Another benefit from plant foods:
Eating these simple foods may slow Alzheimer’s by a third
Brett Arends Dec. 16, 2022
...A long-running and detailed study of nearly 1,000 elderly people has found that those who ate certain foods in their diet—those that contain certain natural compounds known as flavonols—were less likely to get dementia. Seriously less likely.
“The highest quintile of flavonol intake…versus the lowest is associated with a 32% reduction in the rate of cognitive decline,” says Dr. Thomas Holland, an MD and professor at Rush Medical College, who led the study. His study reports that flavonol consumption was “associated with slower decline in global cognition, episodic memory, semantic memory, perceptual speed, and working memory.”...
https://www.marketwatch.com/story/eating-these-simple-foods-may-slow-alzheimers-...
----------------------------------------------------
Thomas Monroe Holland et al. 2022. Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities. Neurology. November 22, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201541 https://n.neurology.org/content/early/2022/11/22/WNL.0000000000201541
Abstract
Background and Objective: Previous research has examined the association between cognition and flavonoids: bioactives found in foods, known to possess anti-inflammatory and antioxidant properties. We extend this research by investigating associations of dietary intakes of total flavonols and constituents (kaempferol, quercetin, myricetin, isorhamnetin) on the change in cognitive performance in global cognition, episodic memory, semantic memory, visuospatial ability, perceptual speed, and working memory
Methods: The study was conducted using 961 participants (60-100 years) of the Rush Memory and Aging Project, a prospective cohort of community-dwelling Chicagoans who were followed for an average of 6.9 years. ...
Results: Higher dietary intake of total flavonols and flavonol constituents were associated with a slower rate of decline in global cognition and multiple cognitive domains. In continuous models adjusted for age, sex, education, APOE-ɛ4, late life cognitive activity, physical activity, and smoking, total flavonol intake was associated with slower decline in global cognition β estimate=0.004..., episodic memory β=0.004 ..., semantic memory β=0.003 ..., perceptual speed β=0.003 ..., and working memory β=0.003 ... and marginally associated with visuospatial ability β=0.001 .... Analyses of individual flavonol constituents demonstrated that intakes of kaempferol and quercetin were associated with slower global cognitive decline {β=0.01... and β=0.004 ...}, respectively. Myricetin and isorhamnetin were not associated with global cognition.
Conclusion: Results suggest dietary intakes of total flavonols and several flavonol constituents may be associated with slower decline in global cognition and multiple cognitive abilities with older age.
_______________________________________________
Healthline: Flavanols
onions
kale
grapes and red wine
tea
peaches
berries
tomatoes
lettuce
scallions
broccoli
https://www.healthline.com/health/what-are-flavonoids-everything-you-need-to-kno...
--------------------------------------------------------
10 Foods High in Quercetin ...
Published: March 2022
Apples – 5 mg per 100 g (roughly half an apple).
Berries
Dark-colored grapes - 3 mg per 100 g (a typical bunch).
Red onions - 39 mg per 100 g (roughly a small onion).
Broccoli (raw) - 3 mg per 100 g (a small bowl).
Kale – 8 mg per 100 g (about a cup).
Capers – 365 mg per 100 g (this may take 2-3 typical servings)
Dill – 55 mg per 100 g (this may take 2-3 typical servings)
Buckwheat – Up to 36 mg per 100 g (about a cup full).
Green tea – 2.63 mg per 100 ml (just under half a cup).
https://www.lifeextension.com/wellness/antioxidants/quercetin-foods
Eating these simple foods may slow Alzheimer’s by a third
Brett Arends Dec. 16, 2022
...A long-running and detailed study of nearly 1,000 elderly people has found that those who ate certain foods in their diet—those that contain certain natural compounds known as flavonols—were less likely to get dementia. Seriously less likely.
“The highest quintile of flavonol intake…versus the lowest is associated with a 32% reduction in the rate of cognitive decline,” says Dr. Thomas Holland, an MD and professor at Rush Medical College, who led the study. His study reports that flavonol consumption was “associated with slower decline in global cognition, episodic memory, semantic memory, perceptual speed, and working memory.”...
https://www.marketwatch.com/story/eating-these-simple-foods-may-slow-alzheimers-...
----------------------------------------------------
Thomas Monroe Holland et al. 2022. Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities. Neurology. November 22, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201541 https://n.neurology.org/content/early/2022/11/22/WNL.0000000000201541
Abstract
Background and Objective: Previous research has examined the association between cognition and flavonoids: bioactives found in foods, known to possess anti-inflammatory and antioxidant properties. We extend this research by investigating associations of dietary intakes of total flavonols and constituents (kaempferol, quercetin, myricetin, isorhamnetin) on the change in cognitive performance in global cognition, episodic memory, semantic memory, visuospatial ability, perceptual speed, and working memory
Methods: The study was conducted using 961 participants (60-100 years) of the Rush Memory and Aging Project, a prospective cohort of community-dwelling Chicagoans who were followed for an average of 6.9 years. ...
Results: Higher dietary intake of total flavonols and flavonol constituents were associated with a slower rate of decline in global cognition and multiple cognitive domains. In continuous models adjusted for age, sex, education, APOE-ɛ4, late life cognitive activity, physical activity, and smoking, total flavonol intake was associated with slower decline in global cognition β estimate=0.004..., episodic memory β=0.004 ..., semantic memory β=0.003 ..., perceptual speed β=0.003 ..., and working memory β=0.003 ... and marginally associated with visuospatial ability β=0.001 .... Analyses of individual flavonol constituents demonstrated that intakes of kaempferol and quercetin were associated with slower global cognitive decline {β=0.01... and β=0.004 ...}, respectively. Myricetin and isorhamnetin were not associated with global cognition.
Conclusion: Results suggest dietary intakes of total flavonols and several flavonol constituents may be associated with slower decline in global cognition and multiple cognitive abilities with older age.
_______________________________________________
Healthline: Flavanols
onions
kale
grapes and red wine
tea
peaches
berries
tomatoes
lettuce
scallions
broccoli
https://www.healthline.com/health/what-are-flavonoids-everything-you-need-to-kno...
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10 Foods High in Quercetin ...
Published: March 2022
Apples – 5 mg per 100 g (roughly half an apple).
Berries
Dark-colored grapes - 3 mg per 100 g (a typical bunch).
Red onions - 39 mg per 100 g (roughly a small onion).
Broccoli (raw) - 3 mg per 100 g (a small bowl).
Kale – 8 mg per 100 g (about a cup).
Capers – 365 mg per 100 g (this may take 2-3 typical servings)
Dill – 55 mg per 100 g (this may take 2-3 typical servings)
Buckwheat – Up to 36 mg per 100 g (about a cup full).
Green tea – 2.63 mg per 100 ml (just under half a cup).
https://www.lifeextension.com/wellness/antioxidants/quercetin-foods
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Some guts are better than others at harvesting energy
University of Copenhagen - Faculty of Science | News Release 25-Dec-2022
...roughly 40 percent of the participants belong to a group that, on average, extracts more energy from food compared to the other 60 percent. The researchers also observed that those who extracted the most energy from food also weighed 10 percent more on average, amounting to an extra nine kilograms.
...The so-called B-type composition (dominated by Bacteroides bacteria) is more effective at extracting nutrients from food and was observed in 40 percent of the participants.
...the food we eat takes a 12-to-36-hour journey, passing several stations along the way, before the body has extracted all the food’s nutrients.
The researchers also studied the length of this journey for each participant, all of whom had similar dietary patterns. Here, the researchers hypothesized that those with long digestive travel times would be the ones who harvested the most nutrition from their food. But the study found the exact opposite....
https://www.eurekalert.org/news-releases/975105
--------------------------------------------------------------------
Jos Boekhorst et al. 2022. Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes. Microbiome volume 10, Article number: 223 (12 Dec 2022). DOI 10.1186/s40168-022-01418-5 https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01418-5
Abstract
Background
It has been hypothesised that the gut microbiota causally affects obesity via its capacity to extract energy from the diet. Yet, evidence elucidating the role of particular human microbial community structures and determinants of microbiota-dependent energy harvest is lacking.
Results
Here, we investigated whether energy extraction from the diet in 85 overweight adults, estimated by dry stool energy density, was associated with intestinal transit time and variations in microbial community diversity and overall structure stratified as enterotypes. We hypothesised that a slower intestinal transit would allow for more energy extraction. However, opposite of what we expected, the stool energy density was positively associated with intestinal transit time. Stratifications into enterotypes showed that individuals with a Bacteroides enterotype (B-type) had significantly lower stool energy density, shorter intestinal transit times, and lower alpha-diversity compared to individuals with a Ruminococcaceae enterotype (R-type). The Prevotella (P-type) individuals appeared in between the B- and R-type. The differences in stool energy density between enterotypes were not explained by differences in habitual diet, intake of dietary fibre or faecal bacterial cell counts. However, the R-type individuals showed higher urinary and faecal levels of microbial-derived proteolytic metabolites compared to the B-type, suggesting increased colonic proteolysis in the R-type individuals. This could imply a less effective colonic energy extraction in the R-type individuals compared to the B-type individuals. Notably, the R-type had significantly lower body weight compared to the B-type.
Conclusions
Our findings suggest that gut microbial energy harvest is diversified among individuals by intestinal transit time and associated gut microbiome ecosystem variations. A better understanding of these associations could support the development of personalised nutrition and improved weight-loss strategies.
University of Copenhagen - Faculty of Science | News Release 25-Dec-2022
...roughly 40 percent of the participants belong to a group that, on average, extracts more energy from food compared to the other 60 percent. The researchers also observed that those who extracted the most energy from food also weighed 10 percent more on average, amounting to an extra nine kilograms.
...The so-called B-type composition (dominated by Bacteroides bacteria) is more effective at extracting nutrients from food and was observed in 40 percent of the participants.
...the food we eat takes a 12-to-36-hour journey, passing several stations along the way, before the body has extracted all the food’s nutrients.
The researchers also studied the length of this journey for each participant, all of whom had similar dietary patterns. Here, the researchers hypothesized that those with long digestive travel times would be the ones who harvested the most nutrition from their food. But the study found the exact opposite....
https://www.eurekalert.org/news-releases/975105
--------------------------------------------------------------------
Jos Boekhorst et al. 2022. Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes. Microbiome volume 10, Article number: 223 (12 Dec 2022). DOI 10.1186/s40168-022-01418-5 https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01418-5
Abstract
Background
It has been hypothesised that the gut microbiota causally affects obesity via its capacity to extract energy from the diet. Yet, evidence elucidating the role of particular human microbial community structures and determinants of microbiota-dependent energy harvest is lacking.
Results
Here, we investigated whether energy extraction from the diet in 85 overweight adults, estimated by dry stool energy density, was associated with intestinal transit time and variations in microbial community diversity and overall structure stratified as enterotypes. We hypothesised that a slower intestinal transit would allow for more energy extraction. However, opposite of what we expected, the stool energy density was positively associated with intestinal transit time. Stratifications into enterotypes showed that individuals with a Bacteroides enterotype (B-type) had significantly lower stool energy density, shorter intestinal transit times, and lower alpha-diversity compared to individuals with a Ruminococcaceae enterotype (R-type). The Prevotella (P-type) individuals appeared in between the B- and R-type. The differences in stool energy density between enterotypes were not explained by differences in habitual diet, intake of dietary fibre or faecal bacterial cell counts. However, the R-type individuals showed higher urinary and faecal levels of microbial-derived proteolytic metabolites compared to the B-type, suggesting increased colonic proteolysis in the R-type individuals. This could imply a less effective colonic energy extraction in the R-type individuals compared to the B-type individuals. Notably, the R-type had significantly lower body weight compared to the B-type.
Conclusions
Our findings suggest that gut microbial energy harvest is diversified among individuals by intestinal transit time and associated gut microbiome ecosystem variations. A better understanding of these associations could support the development of personalised nutrition and improved weight-loss strategies.
122margd
Food for Thought: Early Nutrition Shapes the Brain and Influences What We Like to Eat
Stony Brook University | January 12, 2023
Summary: Study reveals a strong association between what we eat as young children and our food preferences as adults. Findings reveal early gustatory experiences and diet influence brain development.
...{Lead Author Hillary Schiff, Post Doc Stony Brook U} “The presence of a ‘critical period’ of the life cycle for the development of taste preference was a unique and exciting discovery. The prevailing view from other studies prior to this finding was that taste does not have a defined window of heightened sensitivity to experience like other sensory systems such as vision, hearing, and touch.”
The authors maintain that while the study was done in mice, the results inform scientists on the fundamental biological aspects of experiences with taste that extends beyond animal models and to humans.
“The development of taste preference requires a full gustatory experience,” adds {Arianna Maffei, PhD, Senior Author and Professor in the Department of Neurobiology and Behavior}. “This includes the detection of taste in the mouth, its association with smell and the activation of gastrointestinal sensations. All these aspects influence the activity of brain circuits, promoting their healthy development.”...
https://neurosciencenews.com/diet-preference-neurodevelopment-22236/
------------------------------------------------------------
Hillary C. Schiff et al. 202 . Experience-dependent plasticity of gustatory insular cortex circuits and taste preferences. Science Advances 11 Jan 2023. Vol 9, Issue 2. DOI: 10.1126/sciadv.ade6561 https://www.science.org/doi/10.1126/sciadv.ade6561
Abstract
Early experience with food influences taste preference in adulthood. How gustatory experience influences development of taste preferences and refinement of cortical circuits has not been investigated. Here, we exposed weanling mice to an array of taste solutions and determined the effects on the preference for sweet in adulthood. We demonstrate an experience-dependent shift in sucrose preference persisting several weeks following the termination of exposure. A shift in sucrose palatability, altered neural responsiveness to sucrose, and inhibitory synaptic plasticity in the gustatory portion of the insular cortex (GC) were also induced. The modulation of sweet preference occurred within a restricted developmental window, but restoration of the capacity for inhibitory plasticity in adult GC reactivated the sensitivity of sucrose preference to taste experience. Our results establish a fundamental link between gustatory experience, sweet preference, inhibitory plasticity, and cortical circuit function and highlight the importance of early life nutrition in setting taste preferences.
Stony Brook University | January 12, 2023
Summary: Study reveals a strong association between what we eat as young children and our food preferences as adults. Findings reveal early gustatory experiences and diet influence brain development.
...{Lead Author Hillary Schiff, Post Doc Stony Brook U} “The presence of a ‘critical period’ of the life cycle for the development of taste preference was a unique and exciting discovery. The prevailing view from other studies prior to this finding was that taste does not have a defined window of heightened sensitivity to experience like other sensory systems such as vision, hearing, and touch.”
The authors maintain that while the study was done in mice, the results inform scientists on the fundamental biological aspects of experiences with taste that extends beyond animal models and to humans.
“The development of taste preference requires a full gustatory experience,” adds {Arianna Maffei, PhD, Senior Author and Professor in the Department of Neurobiology and Behavior}. “This includes the detection of taste in the mouth, its association with smell and the activation of gastrointestinal sensations. All these aspects influence the activity of brain circuits, promoting their healthy development.”...
https://neurosciencenews.com/diet-preference-neurodevelopment-22236/
------------------------------------------------------------
Hillary C. Schiff et al. 202 . Experience-dependent plasticity of gustatory insular cortex circuits and taste preferences. Science Advances 11 Jan 2023. Vol 9, Issue 2. DOI: 10.1126/sciadv.ade6561 https://www.science.org/doi/10.1126/sciadv.ade6561
Abstract
Early experience with food influences taste preference in adulthood. How gustatory experience influences development of taste preferences and refinement of cortical circuits has not been investigated. Here, we exposed weanling mice to an array of taste solutions and determined the effects on the preference for sweet in adulthood. We demonstrate an experience-dependent shift in sucrose preference persisting several weeks following the termination of exposure. A shift in sucrose palatability, altered neural responsiveness to sucrose, and inhibitory synaptic plasticity in the gustatory portion of the insular cortex (GC) were also induced. The modulation of sweet preference occurred within a restricted developmental window, but restoration of the capacity for inhibitory plasticity in adult GC reactivated the sensitivity of sucrose preference to taste experience. Our results establish a fundamental link between gustatory experience, sweet preference, inhibitory plasticity, and cortical circuit function and highlight the importance of early life nutrition in setting taste preferences.
123margd
...18 January study in Nature of the gut and mouth microbiomes of thousands of people from around the world1 — raises the possibility that diseases linked to microbiome dysfunction, including cancer, diabetes and obesity, could be partly transmissible...
How our microbiome is shaped by family, friends and even neighbours
Social contacts throughout a person’s lifetime seed the body with microbes that could influence health and disease.
Ewen Callaway | 18 January 2023
...strong link between the microbiomes of mothers and those of their children, particularly early in life
...The maternal microbial starter kit has less of an impact on the microbes in people’s mouths, compared with those in their guts. The researchers found that people who lived together — no matter their relationship — tended to have the same microbe strains in their mouths, and the longer they lived together, the more they shared. Couples, however, tended to share strains to a greater extent than did children and parents.
...the extent of household sharing was no less in people from Westernized cultures than it was elsewhere...
https://www.nature.com/articles/d41586-023-00118-w
-----------------------------------------------------
Mireia Valles-Colomer et al. 2023. The person-to-person transmission landscape of the gut and oral microbiomes. Nature (18 January 2023) https://www.nature.com/articles/s41586-022-05620-1
...Conclusion
Our integrative multi-cohort study of microbiome transmission across diverse populations shows extensive previously overlooked person-to-person transmission. This corroborates already suggested hypotheses...and reveals that the transfer of microorganism strains among individuals in long-lasting close contact is a major driver in shaping the personal genetic makeup of the microbiome, and thus of the corresponding metabolic and host–microorganism interaction potential. Although strain sharing was, as expected, greatest between mother and infant gut microbiomes during the first year of life... (median of 50%), shared strains also accounted for 12% and 32% of the gut and oral microbiome species in common between cohabiting individuals, respectively (Figs. 1f and 5a). Such an effect might be induced by close physical interaction even when such interaction started only in adulthood (13% and 38% gut and oral strain sharing between partners respectively; Figs. 3b and 5a) and is partially reversible over long periods, with twins decreasing their initial strain sharing of around 30% to about 10% over 30 years of living apart (Fig. 3c). Because unrelated individuals in different populations or even in different villages of the same population share hardly any strains (0% median strain-sharing rate), our results highlight a non-negligible effect of social interactions in shaping the microbiome, which could have a role in microbiome-associated diseases, and warrants consideration of person-to-person strain transmission in human microbiome studies.
By contrast, we found little influence of divergent lifestyles on microbiome transmission dynamics: despite massive microbiome composition differences in populations loosely defined as westernized or non-westernized34,43,51 on the basis of characteristics such as diet, access to medical facilities and drugs, and hygiene conditions (Methods), we found remarkably similar vertical and horizontal strain-sharing rates. Larger, diverse cohorts and more detailed metadata on participants’ lifestyles and cultural practices are needed to ensure the robustness of this finding, but our results might point to similar microorganism colonization resistance in different populations that could be of greater importance in establishing durable colonization than the intrinsic rates of transmission events. Our results also suggest that the higher richness of microorganisms observed in non-westernized communities...is not promoted by enhanced transmission from other household members, but is rather a consequence of the interaction with the environment as well as diets and lifestyles supporting microorganism diversity.
Species showing particularly high transmissibility (Figs. 2c, 3e, 4c and 5d) should be the starting point for a deeper understanding of the genomic and phenotypic characteristics that can in turn inform transmission mechanisms. Although our study could not resolve whether person-to-person microbiome transmission was direct or its directionality, it provided a systematic overview of microbiome transmission in humans. Further insight into person-to-person microbiome transmission and its directionality could be obtained using specific study designs modelling changes in routine social-interaction networks in humans (for example, following household changes) or in other social animals. The improved strain tracking methods we used that included strain-level profiling of so-far uncultured species...and species-specific definitions of strain based on phylogenetic distances enabled us to scale to large numbers of samples corresponding to more than 800,000 strains. Nonetheless, future studies with whole-genome resolution enabled by deeper sequencing, long-read technologies or single-cell approaches may enable further clarification and refinement of these findings. Overall, our results reinforce the hypothesis that several diseases and conditions that are currently considered non-communicable should be re-evaluated..., and that accounting for transmissibility and social network structure will improve the design of future microbiome investigations and modulation approaches.
How our microbiome is shaped by family, friends and even neighbours
Social contacts throughout a person’s lifetime seed the body with microbes that could influence health and disease.
Ewen Callaway | 18 January 2023
...strong link between the microbiomes of mothers and those of their children, particularly early in life
...The maternal microbial starter kit has less of an impact on the microbes in people’s mouths, compared with those in their guts. The researchers found that people who lived together — no matter their relationship — tended to have the same microbe strains in their mouths, and the longer they lived together, the more they shared. Couples, however, tended to share strains to a greater extent than did children and parents.
...the extent of household sharing was no less in people from Westernized cultures than it was elsewhere...
https://www.nature.com/articles/d41586-023-00118-w
-----------------------------------------------------
Mireia Valles-Colomer et al. 2023. The person-to-person transmission landscape of the gut and oral microbiomes. Nature (18 January 2023) https://www.nature.com/articles/s41586-022-05620-1
...Conclusion
Our integrative multi-cohort study of microbiome transmission across diverse populations shows extensive previously overlooked person-to-person transmission. This corroborates already suggested hypotheses...and reveals that the transfer of microorganism strains among individuals in long-lasting close contact is a major driver in shaping the personal genetic makeup of the microbiome, and thus of the corresponding metabolic and host–microorganism interaction potential. Although strain sharing was, as expected, greatest between mother and infant gut microbiomes during the first year of life... (median of 50%), shared strains also accounted for 12% and 32% of the gut and oral microbiome species in common between cohabiting individuals, respectively (Figs. 1f and 5a). Such an effect might be induced by close physical interaction even when such interaction started only in adulthood (13% and 38% gut and oral strain sharing between partners respectively; Figs. 3b and 5a) and is partially reversible over long periods, with twins decreasing their initial strain sharing of around 30% to about 10% over 30 years of living apart (Fig. 3c). Because unrelated individuals in different populations or even in different villages of the same population share hardly any strains (0% median strain-sharing rate), our results highlight a non-negligible effect of social interactions in shaping the microbiome, which could have a role in microbiome-associated diseases, and warrants consideration of person-to-person strain transmission in human microbiome studies.
By contrast, we found little influence of divergent lifestyles on microbiome transmission dynamics: despite massive microbiome composition differences in populations loosely defined as westernized or non-westernized34,43,51 on the basis of characteristics such as diet, access to medical facilities and drugs, and hygiene conditions (Methods), we found remarkably similar vertical and horizontal strain-sharing rates. Larger, diverse cohorts and more detailed metadata on participants’ lifestyles and cultural practices are needed to ensure the robustness of this finding, but our results might point to similar microorganism colonization resistance in different populations that could be of greater importance in establishing durable colonization than the intrinsic rates of transmission events. Our results also suggest that the higher richness of microorganisms observed in non-westernized communities...is not promoted by enhanced transmission from other household members, but is rather a consequence of the interaction with the environment as well as diets and lifestyles supporting microorganism diversity.
Species showing particularly high transmissibility (Figs. 2c, 3e, 4c and 5d) should be the starting point for a deeper understanding of the genomic and phenotypic characteristics that can in turn inform transmission mechanisms. Although our study could not resolve whether person-to-person microbiome transmission was direct or its directionality, it provided a systematic overview of microbiome transmission in humans. Further insight into person-to-person microbiome transmission and its directionality could be obtained using specific study designs modelling changes in routine social-interaction networks in humans (for example, following household changes) or in other social animals. The improved strain tracking methods we used that included strain-level profiling of so-far uncultured species...and species-specific definitions of strain based on phylogenetic distances enabled us to scale to large numbers of samples corresponding to more than 800,000 strains. Nonetheless, future studies with whole-genome resolution enabled by deeper sequencing, long-read technologies or single-cell approaches may enable further clarification and refinement of these findings. Overall, our results reinforce the hypothesis that several diseases and conditions that are currently considered non-communicable should be re-evaluated..., and that accounting for transmissibility and social network structure will improve the design of future microbiome investigations and modulation approaches.
124margd
Weight loss surgery extends lives, Utah study finds
Sandee LaMotte | Posted - Jan. 28, 2023
...40-year study of nearly 22,000 people who had bariatric surgery in Utah...
Compared with those of similar weight, people who underwent one of four types of weight loss surgery were 16% less likely to die from any cause, (Adams 2023) found. The drop in deaths from diseases triggered by obesity, such as heart disease, cancer and diabetes, was even more dramatic.
"Deaths from cardiovascular disease decreased by 29%, while deaths from various cancers decreased by 43%, which is pretty impressive," said lead author Ted Adams, an adjunct associate professor in nutrition and integrative physiology at the University of Utah's School of Medicine. "There was also a huge percentage drop — a 72% decline — in deaths related to diabetes in people who had surgery compared to those who did not"...One significant downside: The study also found younger people who had the surgery were at higher risk for suicide..."For all-causes of death, the mortality was reduced by 14% for females and by 21% for males," Adams said. In addition, deaths from related causes, such as heart attack, cancer and diabetes, was 24% lower for females and 22% lower for males who underwent surgery compared with those who did not"...
Four types of surgery performed between 1982 and 2018 were examined in the study: gastric bypass, gastric banding, gastric sleeve and duodenal switch...
...(Sjöström 2013) also found a significant number of people were in remission from diabetes at both two years and 10 years after surgery...
https://www.ksl.com/article/50567262/weight-loss-surgery-extends-lives-utah-stud...
-------------------------------------------------
Ted D. Adams et al. 2023. Long-term all-cause and cause-specific mortality for four bariatric surgery procedures. Obesity 25 January 2023
https://doi.org/10.1002/oby.23646 https://onlinelibrary.wiley.com/doi/10.1002/oby.23646
L Sjöström 2013. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med 2013 Mar;273(3):219-34. doi: 10.1111/joim.12012.
Sandee LaMotte | Posted - Jan. 28, 2023
...40-year study of nearly 22,000 people who had bariatric surgery in Utah...
Compared with those of similar weight, people who underwent one of four types of weight loss surgery were 16% less likely to die from any cause, (Adams 2023) found. The drop in deaths from diseases triggered by obesity, such as heart disease, cancer and diabetes, was even more dramatic.
"Deaths from cardiovascular disease decreased by 29%, while deaths from various cancers decreased by 43%, which is pretty impressive," said lead author Ted Adams, an adjunct associate professor in nutrition and integrative physiology at the University of Utah's School of Medicine. "There was also a huge percentage drop — a 72% decline — in deaths related to diabetes in people who had surgery compared to those who did not"...One significant downside: The study also found younger people who had the surgery were at higher risk for suicide..."For all-causes of death, the mortality was reduced by 14% for females and by 21% for males," Adams said. In addition, deaths from related causes, such as heart attack, cancer and diabetes, was 24% lower for females and 22% lower for males who underwent surgery compared with those who did not"...
Four types of surgery performed between 1982 and 2018 were examined in the study: gastric bypass, gastric banding, gastric sleeve and duodenal switch...
...(Sjöström 2013) also found a significant number of people were in remission from diabetes at both two years and 10 years after surgery...
https://www.ksl.com/article/50567262/weight-loss-surgery-extends-lives-utah-stud...
-------------------------------------------------
Ted D. Adams et al. 2023. Long-term all-cause and cause-specific mortality for four bariatric surgery procedures. Obesity 25 January 2023
https://doi.org/10.1002/oby.23646 https://onlinelibrary.wiley.com/doi/10.1002/oby.23646
L Sjöström 2013. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med 2013 Mar;273(3):219-34. doi: 10.1111/joim.12012.
125margd
A Change in Brain Function Contributes to Obesity
Neuroscience · February 6, 2023
University of Calgary researchers find diet-induced obesity is linked to a functional change in the brain.
The study published in Nature Neuroscience finds that in obese mice there is a reduction in function of the brain’s brake signal located in the lateral orbitofrontal cortex. This region of the brain is involved in decision making about rewards and whether action should be taken to get rewards.
“We all change how we value food,” says Dr. Stephanie Borgland, PhD, professor at the Cumming School of Medicine and senior author on the study. “For example, when you’re hungry, a chocolate bar is a high value food. If you were forced to eat five or six chocolate bars though, you would become averse to it. This process is called devaluation.”...
“Our research is confirming that overeating has nothing to do with personal responsibility. It has to do with changes in the way the brain works in response to our food environment,” says Borgland.
The researchers are now conducting a pilot-study to explore the impact of this discovery on humans...
https://neurosciencenews.com/obesity-brain-function-22449/
--------------------------------------------------------------
Lauren T. Seabrook et al. 2023. Disinhibition of the orbitofrontal cortex biases decision-making in obesity. Nature Neuroscience volume 26, pages 92–106 (2023) https://www.nature.com/articles/s41593-022-01210-6
Abstract
The lateral orbitofrontal cortex (lOFC) receives sensory information about food and integrates these signals with expected outcomes to guide future actions, and thus may play a key role in a distributed network of neural circuits that regulate feeding behavior. Here, we reveal a new role for the lOFC in the cognitive control of behavior in obesity. Food-seeking behavior is biased in obesity such that in male obese mice, behaviors are less flexible to changes in the perceived value of the outcome. Obesity is associated with reduced lOFC inhibitory drive and chemogenetic reduction in GABAergic neurotransmission in the lOFC induces obesity-like impairments in goal-directed behavior. Conversely, pharmacological or optogenetic restoration of inhibitory neurotransmission in the lOFC of obese mice reinstates flexible behavior. Our results indicate that obesity-induced disinhibition of the lOFC leads to a failure to update changes in the value of food with satiety, which in turn may influence how individuals make decisions in an obesogenic environment.
Neuroscience · February 6, 2023
University of Calgary researchers find diet-induced obesity is linked to a functional change in the brain.
The study published in Nature Neuroscience finds that in obese mice there is a reduction in function of the brain’s brake signal located in the lateral orbitofrontal cortex. This region of the brain is involved in decision making about rewards and whether action should be taken to get rewards.
“We all change how we value food,” says Dr. Stephanie Borgland, PhD, professor at the Cumming School of Medicine and senior author on the study. “For example, when you’re hungry, a chocolate bar is a high value food. If you were forced to eat five or six chocolate bars though, you would become averse to it. This process is called devaluation.”...
“Our research is confirming that overeating has nothing to do with personal responsibility. It has to do with changes in the way the brain works in response to our food environment,” says Borgland.
The researchers are now conducting a pilot-study to explore the impact of this discovery on humans...
https://neurosciencenews.com/obesity-brain-function-22449/
--------------------------------------------------------------
Lauren T. Seabrook et al. 2023. Disinhibition of the orbitofrontal cortex biases decision-making in obesity. Nature Neuroscience volume 26, pages 92–106 (2023) https://www.nature.com/articles/s41593-022-01210-6
Abstract
The lateral orbitofrontal cortex (lOFC) receives sensory information about food and integrates these signals with expected outcomes to guide future actions, and thus may play a key role in a distributed network of neural circuits that regulate feeding behavior. Here, we reveal a new role for the lOFC in the cognitive control of behavior in obesity. Food-seeking behavior is biased in obesity such that in male obese mice, behaviors are less flexible to changes in the perceived value of the outcome. Obesity is associated with reduced lOFC inhibitory drive and chemogenetic reduction in GABAergic neurotransmission in the lOFC induces obesity-like impairments in goal-directed behavior. Conversely, pharmacological or optogenetic restoration of inhibitory neurotransmission in the lOFC of obese mice reinstates flexible behavior. Our results indicate that obesity-induced disinhibition of the lOFC leads to a failure to update changes in the value of food with satiety, which in turn may influence how individuals make decisions in an obesogenic environment.
126margd
Fructose Could Drive Alzheimer’s Disease
February 13, 2023
Summary: Fructose produced by the brain can lead to inflammation and ultimately Alzheimer’s disease, a new study reports.
Source: University of Colorado
An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer’s disease (AD)...the entire foraging response was set in motion by the metabolism of fructose whether it was eaten or produced in the body. Metabolizing fructose and its byproduct, intracellular uric acid, was critical to the survival of both humans and animals....
Johnson suspects the survival response, what he calls the “survival switch,” that helped ancient humans get through periods of scarcity, is now stuck in the “on” position in a time of relative abundance. This leads to the overeating of high fat, sugary and salty food prompting excess fructose production...
https://neurosciencenews.com/fructose-alzheimers-22490/
------------------------------------------------------------
Richard J. Johnson et al. 2023. Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism? American Journal of Clinical Nutrition. Available online 11 January 2023. In Press, Corrected Proof. https://www.sciencedirect.com/science/article/pii/S0002916523000047
Abstract
An important aspect of survival is to assure enough food, water, and oxygen. Here, we describe a recently discovered response that favors survival in times of scarcity, and it is initiated by either ingestion or production of fructose. Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism and preserve glucose supply for the brain. How this survival mechanism affects brain metabolism, which in a resting human amounts to 20% of the overall energy demand, is only beginning to be understood. Here, we review and extend a previous hypothesis that this survival mechanism has a major role in the development of Alzheimer’s disease and may account for many of the early features, including cerebral glucose hypometabolism, mitochondrial dysfunction, and neuroinflammation. We propose that the pathway can be engaged in multiple ways, including diets high in sugar, high glycemic carbohydrates, and salt. In summary, we propose that Alzheimer’s disease may be the consequence of a maladaptation to an evolutionary-based survival pathway and what had served to enhance survival acutely becomes injurious when engaged for extensive periods. Although more studies are needed on the role of fructose metabolism and its metabolite, uric acid, in Alzheimer’s disease, we suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine whether there is potential benefit in the prevention, management, or treatment of this disease.
February 13, 2023
Summary: Fructose produced by the brain can lead to inflammation and ultimately Alzheimer’s disease, a new study reports.
Source: University of Colorado
An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer’s disease (AD)...the entire foraging response was set in motion by the metabolism of fructose whether it was eaten or produced in the body. Metabolizing fructose and its byproduct, intracellular uric acid, was critical to the survival of both humans and animals....
Johnson suspects the survival response, what he calls the “survival switch,” that helped ancient humans get through periods of scarcity, is now stuck in the “on” position in a time of relative abundance. This leads to the overeating of high fat, sugary and salty food prompting excess fructose production...
https://neurosciencenews.com/fructose-alzheimers-22490/
------------------------------------------------------------
Richard J. Johnson et al. 2023. Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism? American Journal of Clinical Nutrition. Available online 11 January 2023. In Press, Corrected Proof. https://www.sciencedirect.com/science/article/pii/S0002916523000047
Abstract
An important aspect of survival is to assure enough food, water, and oxygen. Here, we describe a recently discovered response that favors survival in times of scarcity, and it is initiated by either ingestion or production of fructose. Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism and preserve glucose supply for the brain. How this survival mechanism affects brain metabolism, which in a resting human amounts to 20% of the overall energy demand, is only beginning to be understood. Here, we review and extend a previous hypothesis that this survival mechanism has a major role in the development of Alzheimer’s disease and may account for many of the early features, including cerebral glucose hypometabolism, mitochondrial dysfunction, and neuroinflammation. We propose that the pathway can be engaged in multiple ways, including diets high in sugar, high glycemic carbohydrates, and salt. In summary, we propose that Alzheimer’s disease may be the consequence of a maladaptation to an evolutionary-based survival pathway and what had served to enhance survival acutely becomes injurious when engaged for extensive periods. Although more studies are needed on the role of fructose metabolism and its metabolite, uric acid, in Alzheimer’s disease, we suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine whether there is potential benefit in the prevention, management, or treatment of this disease.
127margd
Ozempic explained: How weight loss drug works — and what happens if you stop taking it
Ozempic, a diabetes drug, isn’t officially approved for obesity, however doctors are permitted to prescribe it 'off label' for weight management
Sharon Kirkey | Mar 02, 2023
...How much weight can you lose on Ozempic?
In a trial involving nearly 2,000 adults published in the New England Journal of Medicine, people taking semaglutide lost, on average, 15 per cent of their body weight after 68 weeks of treatment, compared to 2.4 per cent for people in the placebo group.
The change in average body weight was 15.3 kg in the semaglutide group, versus 2.6 kg in the placebo. In a subgroup of people who underwent special X-ray imaging of their body composition, the semaglutide arm had less total fat mass and less visceral fat mass, the beer-belly fat that wraps around internal abdominal organs and increases the risk of type 2 diabetes and heart disease.
Of course, not everyone responds. Treatment costs about $5,000 per year. {in Canada?}
What are the side effects of Ozempic?
The drug slows the movement of food through the gut. Nausea and diarrhea are among the most commonly reported side effects, though they’re usually mild-to-moderate and subside with time.
Other side effects can include vomiting, constipation and stomach pain. Possible serious side effects can include inflammation of the pancreas, gallbladder or kidney problems and thyroid tumours, including cancer.
More recently, The New York Times reports that some users are losing any desire for booze. “It’s certainly something that I’ve heard many of patients say, usually in a positive way,” Dr. Robert Gabbay, the chief scientific and medical officer of the American Diabetes Association, told the newspaper.
The belief, though not all the evidence is in, is that semaglutide works on the brain’s mesolimbic system, “the hedonic part of the brain, where you want more than what you need to sustain yourself,” (Dr. Sean Wharton, an obesity medicine specialist and adjunct professor at McMaster University in Hamilton and York University in Toronto, who has led drug-company sponsored studies of semaglutide) said. The hedonic part of the brain is controlled by opioids, cannabinoids, and dopamine. Cravings live there, Wharton said. Cravings for food, alcohol and sex.
If semaglutide works by dialing down food cravings, theoretically it would stand to reason it could suppress other cravings as well, for some, but not all, people.
There is no evidence it decreases sexual desire, Wharton said. “We have not seen that. When people feel healthier, and they have better self-esteem and more confidence, I believe that makes the sexual desire stronger.”
What happens when you stop taking Ozempic?
“You regain the weight,” Wharton said. “And you should, because of what obesity is.”
“I’m not talking about (someone) who is five pounds too high. People living with obesity — excess adipose tissue that’s causing disease — have a genetic condition that drives their eating behaviours.
“That genetic condition will never change. All this medication does is mask that genetic behaviour.”
In a study he helped co-author, researchers found that, one year after stopping their once-weekly semaglutide injections, people regained two-thirds of their prior weight loss.
The findings “confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health,” the researchers wrote.
What is Ozempic face?
So-called Ozempic face “is a silly way of describing weight loss,” Wharton said.
As we get older, we lose the subcutaneous fat in our faces. “If you had excess weight, you may have fat in your face. You lose the weight; the face goes to where it would have been had you never had that excess weight in the first place,” Wharton said.
“It’s the same person the way they genetically would have been if their weight was lower.”
Older diet pill crazes like fen-phen had disastrous results. How can we know history won’t repeat?
The fenfluramine-plus-phentermine regimen was pulled from the market in 1997 after it was discovered the drug combo caused serious heart valve problems.
Three years later, Merida, then a top-selling weight loss drug in Canada, was voluntarily withdrawn over an increased risk of heart attack, stroke and cardiovascular death.
“Is there going to be a problem 15 years from now, 30 years from now? I don’t know,” Wharton said. “But we’re not seeing any (safety) signals.” People need to understand their own individual risk-benefit ratio, he said. Semaglutide has been prescribed to millions of people with type 2 diabetes for 15 years “without any adverse effect profile,” Wharton said.
Is the TikTok celebrity buzz undermining body acceptance?
“Absolutely everybody should be able to live happy, healthy lives,” (Ian Patton, a registered kinesiologist and director of advocacy and public engagement at Obesity Canada) said. “We should have body acceptance and body diversity.
“But a lot of the time it turns into a dichotomy: you can’t have body acceptance, and also talk about effective obesity management for people who require it. And I think that’s wrong.”
People shouldn’t be pushed into any treatment that’s aimed at losing weight or changing their body, he said.
But the social media hype could also be taking away from what the drugs could mean for people with true obesity, he said.
Influencers trying to meet a certain body ideal “don’t really help us progress the narrative around obesity,” Patton said.
https://www.thewhig.com/health/how-ozempic-works
Ozempic, a diabetes drug, isn’t officially approved for obesity, however doctors are permitted to prescribe it 'off label' for weight management
Sharon Kirkey | Mar 02, 2023
...How much weight can you lose on Ozempic?
In a trial involving nearly 2,000 adults published in the New England Journal of Medicine, people taking semaglutide lost, on average, 15 per cent of their body weight after 68 weeks of treatment, compared to 2.4 per cent for people in the placebo group.
The change in average body weight was 15.3 kg in the semaglutide group, versus 2.6 kg in the placebo. In a subgroup of people who underwent special X-ray imaging of their body composition, the semaglutide arm had less total fat mass and less visceral fat mass, the beer-belly fat that wraps around internal abdominal organs and increases the risk of type 2 diabetes and heart disease.
Of course, not everyone responds. Treatment costs about $5,000 per year. {in Canada?}
What are the side effects of Ozempic?
The drug slows the movement of food through the gut. Nausea and diarrhea are among the most commonly reported side effects, though they’re usually mild-to-moderate and subside with time.
Other side effects can include vomiting, constipation and stomach pain. Possible serious side effects can include inflammation of the pancreas, gallbladder or kidney problems and thyroid tumours, including cancer.
More recently, The New York Times reports that some users are losing any desire for booze. “It’s certainly something that I’ve heard many of patients say, usually in a positive way,” Dr. Robert Gabbay, the chief scientific and medical officer of the American Diabetes Association, told the newspaper.
The belief, though not all the evidence is in, is that semaglutide works on the brain’s mesolimbic system, “the hedonic part of the brain, where you want more than what you need to sustain yourself,” (Dr. Sean Wharton, an obesity medicine specialist and adjunct professor at McMaster University in Hamilton and York University in Toronto, who has led drug-company sponsored studies of semaglutide) said. The hedonic part of the brain is controlled by opioids, cannabinoids, and dopamine. Cravings live there, Wharton said. Cravings for food, alcohol and sex.
If semaglutide works by dialing down food cravings, theoretically it would stand to reason it could suppress other cravings as well, for some, but not all, people.
There is no evidence it decreases sexual desire, Wharton said. “We have not seen that. When people feel healthier, and they have better self-esteem and more confidence, I believe that makes the sexual desire stronger.”
What happens when you stop taking Ozempic?
“You regain the weight,” Wharton said. “And you should, because of what obesity is.”
“I’m not talking about (someone) who is five pounds too high. People living with obesity — excess adipose tissue that’s causing disease — have a genetic condition that drives their eating behaviours.
“That genetic condition will never change. All this medication does is mask that genetic behaviour.”
In a study he helped co-author, researchers found that, one year after stopping their once-weekly semaglutide injections, people regained two-thirds of their prior weight loss.
The findings “confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health,” the researchers wrote.
What is Ozempic face?
So-called Ozempic face “is a silly way of describing weight loss,” Wharton said.
As we get older, we lose the subcutaneous fat in our faces. “If you had excess weight, you may have fat in your face. You lose the weight; the face goes to where it would have been had you never had that excess weight in the first place,” Wharton said.
“It’s the same person the way they genetically would have been if their weight was lower.”
Older diet pill crazes like fen-phen had disastrous results. How can we know history won’t repeat?
The fenfluramine-plus-phentermine regimen was pulled from the market in 1997 after it was discovered the drug combo caused serious heart valve problems.
Three years later, Merida, then a top-selling weight loss drug in Canada, was voluntarily withdrawn over an increased risk of heart attack, stroke and cardiovascular death.
“Is there going to be a problem 15 years from now, 30 years from now? I don’t know,” Wharton said. “But we’re not seeing any (safety) signals.” People need to understand their own individual risk-benefit ratio, he said. Semaglutide has been prescribed to millions of people with type 2 diabetes for 15 years “without any adverse effect profile,” Wharton said.
Is the TikTok celebrity buzz undermining body acceptance?
“Absolutely everybody should be able to live happy, healthy lives,” (Ian Patton, a registered kinesiologist and director of advocacy and public engagement at Obesity Canada) said. “We should have body acceptance and body diversity.
“But a lot of the time it turns into a dichotomy: you can’t have body acceptance, and also talk about effective obesity management for people who require it. And I think that’s wrong.”
People shouldn’t be pushed into any treatment that’s aimed at losing weight or changing their body, he said.
But the social media hype could also be taking away from what the drugs could mean for people with true obesity, he said.
Influencers trying to meet a certain body ideal “don’t really help us progress the narrative around obesity,” Patton said.
https://www.thewhig.com/health/how-ozempic-works
128margd
>127 margd: contd.
The New Obesity Breakthrough Drugs
I'm not using the term breakthrough lightly
Eric Topol {cardiologist scientist Scripps} | Dec 10, 2022
...when the two drugs were directly compared in a randomized trial for improving glucose regulation, tirzepatide was superior to semaglutide...
...While there has been a concern about other side effects besides the GI ones noted above, review of all the trials to date in these classes of medication do not reinforce a risk of acute pancreatitis. Other rare side effects that have been noted with these drugs include allergic reactions, gallstones (which can occur with a large amount of weight loss), and potential of medullary thyroid cancer (so far only documented in rats, not people), which is why they are contraindicated in people with Type 2 multiple endocrine neoplasia syndrome.
...Semaglutide is very expensive, ~$1500 per month {in US}, and not covered by Medicare.
...The cost of these drugs will clearly and profoundly exacerbate inequities, since they are eminently affordable by the rich, but the need is extreme among the indigent.
...There are multiple agents in the class under development which should help increase competition and reduce cost, but they will remain expensive. There is private insurance reimbursement, often with a significant copay, for people who tightly fit the inclusion criteria. Eventual coverage by Medicare will markedly expand their use, and we can expect cost-effectiveness studies to be published showing how much saving there is for the drugs compared with bariatric surgery or not achieving the weight loss...
https://erictopol.substack.com/p/the-new-obesity-breakthrough-drugs
The New Obesity Breakthrough Drugs
I'm not using the term breakthrough lightly
Eric Topol {cardiologist scientist Scripps} | Dec 10, 2022
...when the two drugs were directly compared in a randomized trial for improving glucose regulation, tirzepatide was superior to semaglutide...
...While there has been a concern about other side effects besides the GI ones noted above, review of all the trials to date in these classes of medication do not reinforce a risk of acute pancreatitis. Other rare side effects that have been noted with these drugs include allergic reactions, gallstones (which can occur with a large amount of weight loss), and potential of medullary thyroid cancer (so far only documented in rats, not people), which is why they are contraindicated in people with Type 2 multiple endocrine neoplasia syndrome.
...Semaglutide is very expensive, ~$1500 per month {in US}, and not covered by Medicare.
...The cost of these drugs will clearly and profoundly exacerbate inequities, since they are eminently affordable by the rich, but the need is extreme among the indigent.
...There are multiple agents in the class under development which should help increase competition and reduce cost, but they will remain expensive. There is private insurance reimbursement, often with a significant copay, for people who tightly fit the inclusion criteria. Eventual coverage by Medicare will markedly expand their use, and we can expect cost-effectiveness studies to be published showing how much saving there is for the drugs compared with bariatric surgery or not achieving the weight loss...
https://erictopol.substack.com/p/the-new-obesity-breakthrough-drugs
129margd
‘Keto-like’ diet may be associated with a higher risk of heart disease, according to new research
Carma Hassan and Sandee LaMotte | March 6, 2023
...In the study, researchers defined a low-carb, high-fat (LCHF) diet as 45% of total daily calories coming from fat and 25% coming from carbohydrates. The study, which has not been peer reviewed, was presented Sunday at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology...
... The researchers found that people on the LCHF diet had higher levels of low-density lipoprotein, also known as LDL, cholesterol and apolipoprotein B. Apolipoprotein B is a protein that coats LDL cholesterol proteins and can predict heart disease better than elevated levels of LDL cholesterol can.
The researchers also noticed that the LCHF diet participants’ total fat intake was higher in saturated fat and had double the consumption of animal sources (33%) compared to those in the control group (16%).
“After an average of 11.8 years of follow-up – and after adjustment for other risk factors for heart disease, such as diabetes, high blood pressure, obesity and smoking – people on an LCHF diet had more than two-times higher risk of having several major cardiovascular events, such as blockages in the arteries that needed to be opened with stenting procedures, heart attack, stroke and peripheral arterial disease,” researchers found, according to the news release.
...study “can only show an association between the diet and an increased risk for major cardiac events, not a causal relationship,” because it was an observational study, but their findings are worth further study, “especially when approximately 1 in 5 Americans report being on a low-carb, keto-like or full keto diet.”
...The study...looked at the longitudinal effect of following the diet, whereas most people who follow a keto-like diet tend to follow it intermittently for shorter periods of time.
Most of the participants – 73% – were women, which (lead study author Dr. Iulia Iatan with the Healthy Heart Program Prevention Clinic, St. Paul’s Hospital and University of British Columbia’s Centre for Heart Lung Innovation in Vancouver, Canada) said is “quite interesting to see, but it also supports the literature that’s available that women in general tend to follow more dietary patterns, tend to be more interested in changing their lifestyles.”...
... Low-carb diets like keto rely heavily on fats to fill you up. At least 70% of the keto diet will be made up of fat; some say it’s more like 90%.
While you can get all that fat from healthy unsaturated fats such as avocados, tofu, nuts, seeds and olive oil, the diet also allows saturated fats like lard, butter and coconut oil, as well as whole-fat milk, cheese and mayonnaise...
https://www.cnn.com/2023/03/05/health/keto-low-carb-high-fat-diets-heart-disease...
Carma Hassan and Sandee LaMotte | March 6, 2023
...In the study, researchers defined a low-carb, high-fat (LCHF) diet as 45% of total daily calories coming from fat and 25% coming from carbohydrates. The study, which has not been peer reviewed, was presented Sunday at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology...
... The researchers found that people on the LCHF diet had higher levels of low-density lipoprotein, also known as LDL, cholesterol and apolipoprotein B. Apolipoprotein B is a protein that coats LDL cholesterol proteins and can predict heart disease better than elevated levels of LDL cholesterol can.
The researchers also noticed that the LCHF diet participants’ total fat intake was higher in saturated fat and had double the consumption of animal sources (33%) compared to those in the control group (16%).
“After an average of 11.8 years of follow-up – and after adjustment for other risk factors for heart disease, such as diabetes, high blood pressure, obesity and smoking – people on an LCHF diet had more than two-times higher risk of having several major cardiovascular events, such as blockages in the arteries that needed to be opened with stenting procedures, heart attack, stroke and peripheral arterial disease,” researchers found, according to the news release.
...study “can only show an association between the diet and an increased risk for major cardiac events, not a causal relationship,” because it was an observational study, but their findings are worth further study, “especially when approximately 1 in 5 Americans report being on a low-carb, keto-like or full keto diet.”
...The study...looked at the longitudinal effect of following the diet, whereas most people who follow a keto-like diet tend to follow it intermittently for shorter periods of time.
Most of the participants – 73% – were women, which (lead study author Dr. Iulia Iatan with the Healthy Heart Program Prevention Clinic, St. Paul’s Hospital and University of British Columbia’s Centre for Heart Lung Innovation in Vancouver, Canada) said is “quite interesting to see, but it also supports the literature that’s available that women in general tend to follow more dietary patterns, tend to be more interested in changing their lifestyles.”...
... Low-carb diets like keto rely heavily on fats to fill you up. At least 70% of the keto diet will be made up of fat; some say it’s more like 90%.
While you can get all that fat from healthy unsaturated fats such as avocados, tofu, nuts, seeds and olive oil, the diet also allows saturated fats like lard, butter and coconut oil, as well as whole-fat milk, cheese and mayonnaise...
https://www.cnn.com/2023/03/05/health/keto-low-carb-high-fat-diets-heart-disease...
130margd
"Eat Less, Move More" Doesn't Actually Work for Weight Loss, According to a New Study
This superficial advice may do more harm than good, a new study suggests. If you actually want to see the scale shift, here's what to keep in mind.
Karla Walsh | December 15, 2022
https://www.eatingwell.com/article/8019040/eat-less-move-more-doesnt-work-for-we...
-----------------------------------------------------------------
Madeleine Tremblett et al. 2022. What advice do general practitioners give to people living with obesity to lose weight? A qualitative content analysis of recorded interactions. Family Practice, cmac137, https://doi.org/10.1093/fampra/cmac137
Published: 13 December 2022. https://academic.oup.com/fampra/advance-article/doi/10.1093/fampra/cmac137/68495...
Abstract
Background
Guidelines recommend general practitioners (GPs) take every opportunity to talk to people living with obesity about their weight, and evidence shows even very brief advice is associated with weight loss. However, little is known about what GPs say when giving brief behavioural advice, and if it reflects evidence-based recommendations for people living with obesity. To understand what behavioural advice GPs give, we categorized the content and delivery of GPs’ advice during brief interventions.
Methods
Qualitative content analysis was applied to 159 audio recordings of consultations from the Brief Interventions for Weight Loss (BWeL) trial, where GPs gave brief weight-loss advice to patients with a body mass index ≥30 kg/m2 (or ≥25 kg/m2 if Asian) in 137 UK surgeries. Similar content was grouped into descriptive clusters.
Results
The results comprised 4 clusters, illuminating different aspects of the advice given: (i) Content of diet and physical activity advice, showing this was highly varied; (ii) Content of “implementation tips” given to support changes, e.g. using smaller plates; (iii) Content of signposting support, either towards further clinician support, or other resources, e.g. information booklets; (iv) Style of advice delivery, showing GPs rarely gave personalized advice, or reasons for their advice.
Conclusions and implications
Weight-loss advice from GPs to patients with obesity rarely included effective methods, mostly communicating a general “eat less, do more” approach. Advice was mostly generic, and rarely tailored to patients’ existing knowledge and behaviours. Effectiveness of brief weight-loss advice could be improved if GPs were given clearer guidance on evidence-based recommendations.
This superficial advice may do more harm than good, a new study suggests. If you actually want to see the scale shift, here's what to keep in mind.
Karla Walsh | December 15, 2022
https://www.eatingwell.com/article/8019040/eat-less-move-more-doesnt-work-for-we...
-----------------------------------------------------------------
Madeleine Tremblett et al. 2022. What advice do general practitioners give to people living with obesity to lose weight? A qualitative content analysis of recorded interactions. Family Practice, cmac137, https://doi.org/10.1093/fampra/cmac137
Published: 13 December 2022. https://academic.oup.com/fampra/advance-article/doi/10.1093/fampra/cmac137/68495...
Abstract
Background
Guidelines recommend general practitioners (GPs) take every opportunity to talk to people living with obesity about their weight, and evidence shows even very brief advice is associated with weight loss. However, little is known about what GPs say when giving brief behavioural advice, and if it reflects evidence-based recommendations for people living with obesity. To understand what behavioural advice GPs give, we categorized the content and delivery of GPs’ advice during brief interventions.
Methods
Qualitative content analysis was applied to 159 audio recordings of consultations from the Brief Interventions for Weight Loss (BWeL) trial, where GPs gave brief weight-loss advice to patients with a body mass index ≥30 kg/m2 (or ≥25 kg/m2 if Asian) in 137 UK surgeries. Similar content was grouped into descriptive clusters.
Results
The results comprised 4 clusters, illuminating different aspects of the advice given: (i) Content of diet and physical activity advice, showing this was highly varied; (ii) Content of “implementation tips” given to support changes, e.g. using smaller plates; (iii) Content of signposting support, either towards further clinician support, or other resources, e.g. information booklets; (iv) Style of advice delivery, showing GPs rarely gave personalized advice, or reasons for their advice.
Conclusions and implications
Weight-loss advice from GPs to patients with obesity rarely included effective methods, mostly communicating a general “eat less, do more” approach. Advice was mostly generic, and rarely tailored to patients’ existing knowledge and behaviours. Effectiveness of brief weight-loss advice could be improved if GPs were given clearer guidance on evidence-based recommendations.
131margd
Mouse study study below had me googling VMH (hypothalamus) virus (lots of studies) as well as the amino acid, D-serine. "D-serine supplement rescued cognitive decline in aged mice." Also useful in treating schizophrenia?
Lige Leng et al. 2023. Hypothalamic Menin regulates systemic aging and cognitive decline.
PLOS Biology. March 16, 2023. https://doi.org/10.1371/journal.pbio.3002033 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002033#se...
Abstract
Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits.
Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.
------------------------------------------------------------------
D-serine
https://examine.com/supplements/d-serine/#dosage-information
Lige Leng et al. 2023. Hypothalamic Menin regulates systemic aging and cognitive decline.
PLOS Biology. March 16, 2023. https://doi.org/10.1371/journal.pbio.3002033 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002033#se...
Abstract
Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits.
Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.
------------------------------------------------------------------
D-serine
https://examine.com/supplements/d-serine/#dosage-information
132margd
Can Mothers Pass Obesity on to Daughters?
— Approaches to addressing body weight and composition should start early in life, researcher says
Kristen Monaco, Staff Writer, MedPage Today | March 21, 2023
...Of note, at no age was daughters' BMI or fat mass significantly linked with paternal BMI or fat mass. Furthermore, at no age was boys' BMI or fat mass linked with either maternal or paternal BMI or fat mass...
https://www.medpagetoday.com/endocrinology/obesity/103638
----------------------------------------------------------------
Rebecca J Moon et al. 2023. Parent-Offspring Associations in Body Composition: Findings From the Southampton Women's Survey Prospective Cohort Study. The Journal of Clinical Endocrinology & Metabolism, dgad128,
Published: 21 March 2023. (Corrected Proof) https://doi.org/10.1210/clinem/dgad128 https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgad12...
Abstract
...Results
Positive associations between mother-daughter body mass index (BMI) and fat mass were observed at ages 6 to 7 (BMI: β = .29 SD/SD...; fat mass β = .27 SD/SD) and 8 to 9 years (BMI: β = .33 SD/SD...; fat mass β = .31 SD/SD..., with similar associations at age 4 years but bounding the 95% CI. The mother-son, father-son, and father-daughter associations for BMI and fat mass were weaker at each of the ages studied.
Conclusion
A strong association between the fat mass of mothers and their daughters but not their sons was observed. In contrast, father-offspring body composition associations were not evident. The dimorphic parent-offspring effects suggest particular attention should be given to early prevention of unfavorable body composition in girls born to mothers with excess adiposity.
— Approaches to addressing body weight and composition should start early in life, researcher says
Kristen Monaco, Staff Writer, MedPage Today | March 21, 2023
...Of note, at no age was daughters' BMI or fat mass significantly linked with paternal BMI or fat mass. Furthermore, at no age was boys' BMI or fat mass linked with either maternal or paternal BMI or fat mass...
https://www.medpagetoday.com/endocrinology/obesity/103638
----------------------------------------------------------------
Rebecca J Moon et al. 2023. Parent-Offspring Associations in Body Composition: Findings From the Southampton Women's Survey Prospective Cohort Study. The Journal of Clinical Endocrinology & Metabolism, dgad128,
Published: 21 March 2023. (Corrected Proof) https://doi.org/10.1210/clinem/dgad128 https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgad12...
Abstract
...Results
Positive associations between mother-daughter body mass index (BMI) and fat mass were observed at ages 6 to 7 (BMI: β = .29 SD/SD...; fat mass β = .27 SD/SD) and 8 to 9 years (BMI: β = .33 SD/SD...; fat mass β = .31 SD/SD..., with similar associations at age 4 years but bounding the 95% CI. The mother-son, father-son, and father-daughter associations for BMI and fat mass were weaker at each of the ages studied.
Conclusion
A strong association between the fat mass of mothers and their daughters but not their sons was observed. In contrast, father-offspring body composition associations were not evident. The dimorphic parent-offspring effects suggest particular attention should be given to early prevention of unfavorable body composition in girls born to mothers with excess adiposity.
133margd
Obesity Tied to Density of Food Stores Carrying Less Healthy Options, Report Finds
— Link between obesity and unhealthy food establishments holds in both rural and non-rural areas
Joyce Frieden, Washington Editor, MedPage Today | March 21, 2023
...Clinicians can use the study as a reminder of the varied contributors to their patients' diets, Waxman said. "Healthcare professionals are often in the position of advising patients to eat better, and often there's not enough recognition in the healthcare sector of what the barriers are -- that might be affordability and also just what's in your environment. It's not enough to think of it as an individual health issue -- it also is a population-wide issue."
In that regard, "there are definitely communities where healthcare systems have begun to step up in areas of affordable housing, recognizing that's an important source of stability, and to get people on SNAP (Supplemental Nutrition Assistance Program, formerly known as food stamps)," she said. "And if you're in a rural hospital or serving a community of color where (food) options are limited, you can be in the conversation about what the community response is."
Policymakers also can come at this issue in several ways, Waxman said. For instance, the U.S. Department of Agriculture operates the Gus Schumacher Nutrition Incentive Program (GusNIP), a competitive grant program that pays states and localities to increase the value of SNAP benefits when used to purchase fruits and vegetables. Although many GusNIP programs are already in areas with high rates of obesity, other such areas don't have the program yet, she said.
Healthy food financing investments to bring in stores selling healthy food is another option, and local lawmakers also can consider adopting zoning laws that favor healthy food establishments over unhealthy ones, as some places have done.
https://www.medpagetoday.com/endocrinology/obesity/103641
----------------------------------------------------------------
Elaine Waxman et al. 2023. Retail Food Access and Obesity Prevalence: Mapping Variation across the United States (Research Report). Urban Institute. March 13, 2023. https://www.urban.org/research/publication/retail-food-access-and-obesity-preval...
...While obesity is widespread in the US, it is not distributed equally across places. The highest obesity rates in the US are concentrated in Southern counties, particularly those in parts of Texas, Louisiana, Mississippi, Kentucky, and West Virginia. In contrast, the lowest obesity rates are concentrated in Western counties, especially those in Colorado and parts of Wyoming, California, and Nevada.
On average, counties with high obesity rates have more food establishments per 1,000 residents than counties with low obesity rates.
We find stark differences in the mix of food establishment types between low-, middle-, and high-obesity counties when we categorize food establishments by whether they are likely to serve healthy or unhealthy food. Among all food establishments, 65.5 percent are considered likely unhealthy in counties with a high percentage of residents with obesity compared with 51.5 percent in counties with a low percentage of residents with obesity. This pattern holds even after controlling for a variety of other county-level characteristics.
Food establishments more likely to serve unhealthy foods are largely comprised of convenience stores, followed by gas stations, dollar stores, and pharmacies in both low- and high-obesity counties. However, dollar stores represent a substantially larger share of unhealthy food establishments in high-obesity areas than in low-obesity areas...
— Link between obesity and unhealthy food establishments holds in both rural and non-rural areas
Joyce Frieden, Washington Editor, MedPage Today | March 21, 2023
...Clinicians can use the study as a reminder of the varied contributors to their patients' diets, Waxman said. "Healthcare professionals are often in the position of advising patients to eat better, and often there's not enough recognition in the healthcare sector of what the barriers are -- that might be affordability and also just what's in your environment. It's not enough to think of it as an individual health issue -- it also is a population-wide issue."
In that regard, "there are definitely communities where healthcare systems have begun to step up in areas of affordable housing, recognizing that's an important source of stability, and to get people on SNAP (Supplemental Nutrition Assistance Program, formerly known as food stamps)," she said. "And if you're in a rural hospital or serving a community of color where (food) options are limited, you can be in the conversation about what the community response is."
Policymakers also can come at this issue in several ways, Waxman said. For instance, the U.S. Department of Agriculture operates the Gus Schumacher Nutrition Incentive Program (GusNIP), a competitive grant program that pays states and localities to increase the value of SNAP benefits when used to purchase fruits and vegetables. Although many GusNIP programs are already in areas with high rates of obesity, other such areas don't have the program yet, she said.
Healthy food financing investments to bring in stores selling healthy food is another option, and local lawmakers also can consider adopting zoning laws that favor healthy food establishments over unhealthy ones, as some places have done.
https://www.medpagetoday.com/endocrinology/obesity/103641
----------------------------------------------------------------
Elaine Waxman et al. 2023. Retail Food Access and Obesity Prevalence: Mapping Variation across the United States (Research Report). Urban Institute. March 13, 2023. https://www.urban.org/research/publication/retail-food-access-and-obesity-preval...
...While obesity is widespread in the US, it is not distributed equally across places. The highest obesity rates in the US are concentrated in Southern counties, particularly those in parts of Texas, Louisiana, Mississippi, Kentucky, and West Virginia. In contrast, the lowest obesity rates are concentrated in Western counties, especially those in Colorado and parts of Wyoming, California, and Nevada.
On average, counties with high obesity rates have more food establishments per 1,000 residents than counties with low obesity rates.
We find stark differences in the mix of food establishment types between low-, middle-, and high-obesity counties when we categorize food establishments by whether they are likely to serve healthy or unhealthy food. Among all food establishments, 65.5 percent are considered likely unhealthy in counties with a high percentage of residents with obesity compared with 51.5 percent in counties with a low percentage of residents with obesity. This pattern holds even after controlling for a variety of other county-level characteristics.
Food establishments more likely to serve unhealthy foods are largely comprised of convenience stores, followed by gas stations, dollar stores, and pharmacies in both low- and high-obesity counties. However, dollar stores represent a substantially larger share of unhealthy food establishments in high-obesity areas than in low-obesity areas...
134margd
Novel Drug Makes Mice Skinny Even on Sugary, Fatty Diet
FeaturedNeuroscienceOpen Neuroscience Articles
·March 21, 2023
Summary: Researchers have developed a new molecule that limits magnesium transport in mitochondria. The drug prevents weight gain and liver damage in mice who were fed a high-sugar, Western-style diet since birth. After exposure to the molecule, overweight mice started to lose weight.
Source: UT Health San Antonio
Researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have developed a small-molecule drug that prevents weight gain and adverse liver changes in mice fed a high-sugar, high-fat Western diet throughout life.
https://neurosciencenews.com/weight-reduction-molecule-22845/
------------------------------------------------------------------
Travis R. Madaris et al. 2023. Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress. Cell Reports Volume 42, ISSUE 3, 112155, March 28, 2023 DOI:https://doi.org/10.1016/j.celrep.2023.112155 https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00166-3
Highlights
• Mitochondrial Mg2+ channel Mrs2 rheostats MCU Ca2+ signals to maintain bioenergetic circuit
• DNL precursor and cellular Mg2+ chelator citrate curbs HIF1α signal and oxidative metabolism
• Lowering mMg2+ mitigates prolonged dietary-stress-induced obesity and metabolic syndrome
• Mrs2 channel blocker CPACC reduces lipid accumulation and promotes browning and weight loss
Summary
The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-μM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, β-oxidation, thermogenesis, and HIF-1α-targets, in Mrs2−/− mice that are further enhanced under Western-diet-associated metabolic stress. Thus, lowering mMg2+ promotes metabolism and dampens diet-induced obesity and metabolic syndrome.
FeaturedNeuroscienceOpen Neuroscience Articles
·March 21, 2023
Summary: Researchers have developed a new molecule that limits magnesium transport in mitochondria. The drug prevents weight gain and liver damage in mice who were fed a high-sugar, Western-style diet since birth. After exposure to the molecule, overweight mice started to lose weight.
Source: UT Health San Antonio
Researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have developed a small-molecule drug that prevents weight gain and adverse liver changes in mice fed a high-sugar, high-fat Western diet throughout life.
https://neurosciencenews.com/weight-reduction-molecule-22845/
------------------------------------------------------------------
Travis R. Madaris et al. 2023. Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress. Cell Reports Volume 42, ISSUE 3, 112155, March 28, 2023 DOI:https://doi.org/10.1016/j.celrep.2023.112155 https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00166-3
Highlights
• Mitochondrial Mg2+ channel Mrs2 rheostats MCU Ca2+ signals to maintain bioenergetic circuit
• DNL precursor and cellular Mg2+ chelator citrate curbs HIF1α signal and oxidative metabolism
• Lowering mMg2+ mitigates prolonged dietary-stress-induced obesity and metabolic syndrome
• Mrs2 channel blocker CPACC reduces lipid accumulation and promotes browning and weight loss
Summary
The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-μM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, β-oxidation, thermogenesis, and HIF-1α-targets, in Mrs2−/− mice that are further enhanced under Western-diet-associated metabolic stress. Thus, lowering mMg2+ promotes metabolism and dampens diet-induced obesity and metabolic syndrome.
135margd
Sweets Change Our Brain: Why Sweet Foods Are Irresistible
FeaturedNeuroscience
·March 22, 2023
Summary: Consuming high-fat and high-sugar foods causes changes in activity and connectivity in the brain’s dopaminergic system, resulting in a stronger preference for these foods.
Source: Max Planck Institute
Chocolate bars, crisps and fries—why can’t we just ignore them in the supermarket?
Researchers at the Max Planck Institute for Metabolism Research in Cologne, in collaboration with Yale University, have now shown that foods with a high fat and sugar content change our brain: If we regularly eat even small amounts of them, the brain learns to consume precisely these foods in the future...
https://neurosciencenews.com/sweet-food-brain-changes-22847/
------------------------------------------------------------------
Sharmili Edwin Thanarajah et al. 2023. Habitual daily intake of a sweet and fatty snack modulates reward processing in humans (Corrected proof). Cell Metabolism 22 March 2023. https://www.sciencedirect.com/science/article/pii/S1550413123000517?via%3Dihub
...Results
Metabolic state and general dietary pattern remained unchanged after HF/HS {high fat/high sugar, e.g., pudding, apple juice} intervention...
Taste perception of fattiness and sweetness was preserved after HF/HS intervention...
HF/HS intervention altered fat preference
{fat preference is acquired?}
HF/HS and LF/LS interventions reduced preference (wanting) for low sucrose concentrations
{sounds like craving for sugar is hard-wired?}
HF/HS intervention {milkshakes} enhanced neural responses to food anticipation and consumption
FeaturedNeuroscience
·March 22, 2023
Summary: Consuming high-fat and high-sugar foods causes changes in activity and connectivity in the brain’s dopaminergic system, resulting in a stronger preference for these foods.
Source: Max Planck Institute
Chocolate bars, crisps and fries—why can’t we just ignore them in the supermarket?
Researchers at the Max Planck Institute for Metabolism Research in Cologne, in collaboration with Yale University, have now shown that foods with a high fat and sugar content change our brain: If we regularly eat even small amounts of them, the brain learns to consume precisely these foods in the future...
https://neurosciencenews.com/sweet-food-brain-changes-22847/
------------------------------------------------------------------
Sharmili Edwin Thanarajah et al. 2023. Habitual daily intake of a sweet and fatty snack modulates reward processing in humans (Corrected proof). Cell Metabolism 22 March 2023. https://www.sciencedirect.com/science/article/pii/S1550413123000517?via%3Dihub
...Results
Metabolic state and general dietary pattern remained unchanged after HF/HS {high fat/high sugar, e.g., pudding, apple juice} intervention...
Taste perception of fattiness and sweetness was preserved after HF/HS intervention...
HF/HS intervention altered fat preference
{fat preference is acquired?}
HF/HS and LF/LS interventions reduced preference (wanting) for low sucrose concentrations
{sounds like craving for sugar is hard-wired?}
HF/HS intervention {milkshakes} enhanced neural responses to food anticipation and consumption
136margd
Synaptic Plasticity May Affect Diet Outcomes
Max Planck Institute | March 24, 2023
Summary: When dieting, hunger-mediating AgRP neurons receive stronger signals, inducing synaptic plasticity. This may explain why people tend to eat more after a diet and regain the weight they have lost.
Many people who have dieted are familiar with the yo-yo effect: after the diet, the kilos are quickly put back on...
https://neurosciencenews.com/synaptic-plasticity-diet-22859/
---------------------------------------------------------------
Katarzyna Grzelka et al. 2023. A synaptic amplifier of hunger for regaining body weight in the hypothalamus. Cell Metabolism. Available online 24 March 2023. In Press, Corrected Proof. https://doi.org/10.1016/j.cmet.2023.03.002 https://www.sciencedirect.com/science/article/pii/S1550413123000803?via%3Dihub
Highlights
• Weight loss upon caloric deprivation activates PVHTRH neurons that co-express PACAP
• Activated PVHTRH neurons increase the number of active PVHTRH → AgRP neuron synapses
• Potentiation of excitatory PVHTRH → AgRP synapses lasts until lost weight is regained
• PVHTRH → AgRP circuit activity is necessary and sufficient for driving weight (re)gain
Summary
...We reveal a crucial role for activity-dependent, remarkably long-lasting amplification of synaptic activity originating from paraventricular hypothalamus thyrotropin-releasing (PVHTRH) neurons in long-term body weight control. Silencing PVHTRH neurons inhibits the potentiation of excitatory input to AgRP neurons and diminishes concomitant regain of lost weight. Brief stimulation of the pathway is sufficient to enduringly potentiate this glutamatergic hunger synapse and triggers an NMDAR-dependent gaining of body weight that enduringly persists. Identification of this activity-dependent synaptic amplifier provides a previously unrecognized target to combat regain of lost weight.
Max Planck Institute | March 24, 2023
Summary: When dieting, hunger-mediating AgRP neurons receive stronger signals, inducing synaptic plasticity. This may explain why people tend to eat more after a diet and regain the weight they have lost.
Many people who have dieted are familiar with the yo-yo effect: after the diet, the kilos are quickly put back on...
https://neurosciencenews.com/synaptic-plasticity-diet-22859/
---------------------------------------------------------------
Katarzyna Grzelka et al. 2023. A synaptic amplifier of hunger for regaining body weight in the hypothalamus. Cell Metabolism. Available online 24 March 2023. In Press, Corrected Proof. https://doi.org/10.1016/j.cmet.2023.03.002 https://www.sciencedirect.com/science/article/pii/S1550413123000803?via%3Dihub
Highlights
• Weight loss upon caloric deprivation activates PVHTRH neurons that co-express PACAP
• Activated PVHTRH neurons increase the number of active PVHTRH → AgRP neuron synapses
• Potentiation of excitatory PVHTRH → AgRP synapses lasts until lost weight is regained
• PVHTRH → AgRP circuit activity is necessary and sufficient for driving weight (re)gain
Summary
...We reveal a crucial role for activity-dependent, remarkably long-lasting amplification of synaptic activity originating from paraventricular hypothalamus thyrotropin-releasing (PVHTRH) neurons in long-term body weight control. Silencing PVHTRH neurons inhibits the potentiation of excitatory input to AgRP neurons and diminishes concomitant regain of lost weight. Brief stimulation of the pathway is sufficient to enduringly potentiate this glutamatergic hunger synapse and triggers an NMDAR-dependent gaining of body weight that enduringly persists. Identification of this activity-dependent synaptic amplifier provides a previously unrecognized target to combat regain of lost weight.
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Beige Fat Could Hold Key to Age-Related Metabolism Change
Becka Bowyer · April 6, 2023
Summary: Stimulating the production of white adipose tissue, or beige fat, helps to reverse a slowing metabolism. The findings could help ward off age-related weight gain and prevent metabolism disorders.
...shows therapeutic promise in a third type of fat, a subtype of WAT (White Adipose Tissue): beige fat. Beige fat has the same cellular precursors as white fat and the same thermogenic properties as brown fat, which means it helps to reduce blood sugar and the fatty acids that cause hardening of the arteries and heart disease.
When a person experiences sustained exposure to cold temperatures, stem cells known as adipose progenitor cells form thermogenic beige fat cells within white fat. As people age, the response to that stimulus weakens, tipping the balance toward white fat production.
“There are seasonal changes in beige fat in young humans,” said Dan Berry, assistant professor in the Division of Nutritional Sciences, “but an older person would have to stand outside in the snow in their underwear to get those same effects.”
...In the paper, they reveal the role of a specific signaling pathway that suppresses beige fat formation in older mice by antagonizing the immune system. By suppressing that pathway in aging mice, the scientists were able to prompt beige fat production in animals that otherwise formed only in WAT...
Original Research: Open access. "Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice” by Dan Berry et al. Nature Communications. https://www.nature.com/articles/s41467-023-37386-z
https://neurosciencenews.com/beige-fat-metabolism-22953/
Becka Bowyer · April 6, 2023
Summary: Stimulating the production of white adipose tissue, or beige fat, helps to reverse a slowing metabolism. The findings could help ward off age-related weight gain and prevent metabolism disorders.
...shows therapeutic promise in a third type of fat, a subtype of WAT (White Adipose Tissue): beige fat. Beige fat has the same cellular precursors as white fat and the same thermogenic properties as brown fat, which means it helps to reduce blood sugar and the fatty acids that cause hardening of the arteries and heart disease.
When a person experiences sustained exposure to cold temperatures, stem cells known as adipose progenitor cells form thermogenic beige fat cells within white fat. As people age, the response to that stimulus weakens, tipping the balance toward white fat production.
“There are seasonal changes in beige fat in young humans,” said Dan Berry, assistant professor in the Division of Nutritional Sciences, “but an older person would have to stand outside in the snow in their underwear to get those same effects.”
...In the paper, they reveal the role of a specific signaling pathway that suppresses beige fat formation in older mice by antagonizing the immune system. By suppressing that pathway in aging mice, the scientists were able to prompt beige fat production in animals that otherwise formed only in WAT...
Original Research: Open access. "Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice” by Dan Berry et al. Nature Communications. https://www.nature.com/articles/s41467-023-37386-z
https://neurosciencenews.com/beige-fat-metabolism-22953/
138margd
Obesity: Men and women have different drivers that lead to weight gain
Paul Ian Cross | April 13, 2023
...The (MRI) analysis was able to correctly differentiate high BMI from normal BMI participants and males with high BMI from females with high BMI with 77% and 75% accuracy, respectively.
...(Dr. Arpana Gupta, associate professor at the David Geffen School of Medicine at UCLA and lead author of the study) noted that women with obesity exhibited changes in emotion-related brain regions that were linked to higher levels of compulsive eating. Meanwhile, in men, brain regions related to eating behavior and obesity were associated with gut and visceral sensations linked to abdominal discomfort and hunger...
https://www.medicalnewstoday.com/articles/obesity-men-and-women-have-different-d...
----------------------------------------------
Ravi R Bhatt et al. 2023. Integrated multimodal brain signatures predict sex-specific obesity status (Accepted Manuscript). Brain Communications Published: 04 April 2023 https://doi.org/10.1093/braincomms/fcad098 https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcad0...
Abstract
... models differentiated high BMI against non-obese BMI participants, and males with high BMI against females with high BMI obtaining balanced accuracies of 77% and 75% respectively. Sex-specific differences within the cortico-basal-ganglia-thalamic-cortico loop, the choroid plexus-cereberospinal fluid system, salience, sensorimotor and deafult-mode networks were identified, and were associated with early life adversity, mental health quality, and greater somatosensation. Results showed multi-modal brain signatures suggesting sex-specific cortical mechanisms underlying obesity, which fosters clinical implications for tailored obesity interventions based on sex.
Discussion
The objective of the study was to examine sex differences in brain networks related to obesity.
The main findings of the study were: 1) greater choroid plexus and ventricular and volume in high
BMI individuals was associated with anatomical connectivity alterations in the cortico-basal
ganglia-thalamo-cortical loop; 2) greater early life trauma was associated with greater volume and
surface area and anatomical connectivity of the anterior insula and greater sensorimotor-DMN
resting-state connectivity; 3) compared to males with high BMI, females with high BMI showed
lower mental health scores which was associated with lower amygdala resting-state functional
connectivity to the SMN; 4) and compared to males with high BMI, females with high BMI had
greater PILL scores which were associated with lower surface area and volume in the anterior
cingulate cortex. Our results provide a sex-specific biological marker that could explain the short-
term feeding regulation and sensory processing patterns seen in females with obesity. To our
knowledge, this is the first study to utilize a data-driven approach to predict the sex-specific obesity
status of an individual based on multimodal brain signatures.
BMI-Dependent Effects on Brain
Individuals with high BMI displayed lower connectivity within the cortico-basal-ganglia-thalamo-cortico (CBGTC) loop which was associated with greater bilateral lateral ventricle volume. The CBGTC loop plays a key role in the reward circuitry, and in the context of obesity is known to receive dopaminergic input from the ventral tegmental area and substantia nigra to regulate motivational and incentive properties of food.66 Altered white matter properties in this
loop have been shown repeatedly,67 and lower count of white matter tracts within this circuitry can translate to the individual being less efficiently being able to regulate food intake beyond hemostatic needs. Our results showed changes in many regions of the brain which respond to food or food-associated cues66 and were highly correlated with early life trauma... ... In the context of obesity, those with early life trauma may suggest a risk factor for a consistently active threat response, as observed in individuals with obesity indexed via psychophysiological
parameters.69
The current results show greater choroid plexus and ventricle volume in those with high BMI. ... insulin is produced by ependymal cells of the choroid plexus ...dense expression of leptin receptors in the choroid plexus71 and its role in transporting leptin into the brain across the blood brain barrier,72 suggests the current results of greater choroid plexus and ventricle volume may be directly reflective of the amount of adipose tissue in the body.73 Leptin and insulin are known to be very high in obese individuals due to the resistantance that develops over time. The body compensates by releasing more of these hormones,74,75 which has the potential to be reflected via larger choroid plexus and ventricular volumes...yhose with high BMI had greater anatomical connectivity between the vmPFC and anterior insula, along with greater surface area of the anterior insula, where much of hedonic value processing is conducted.66 Moreover, the current results may suggest accelerated aging in those with high BMI, as greater ventricular volume in the context of aging has been associated with greater BMI...
Sex-Specific and-BMI Effects on Brain
Compared to males with high BMI, females with high BMI showed lower scores on the mental health subscale of the SF-12, which was highly correlated to lower resting-state connectivity between the amygdala and various regions of the sensorimotor network. These regions of the sensorimotor network also had greater mean curvature. Lower connectivity between the amygdala and sensorimotor network was associated with greater anxiety and lower resilience, both of which were observed in females with high BMI. Regions in the sensorimotor network, have been implicated in inappropriate cognitive evaluations of incoming sensory stimuli, resulting in an increased motivational reward placed on food-related stimuli, especially in females compared to males.79,80 ...Lower connectivity between the amygdala and this established sensorimotor network in women with high BMI compared to males suggests that females may have a reduced capacity to integrate emotions with action directed goal planning, resulting in greater “emotional overeating” compared to males.83,84 ... lower mental health scores in females with high BMI compared to males with high BMI.
Females with high BMI compared to males with high BMI also had greater PILL (Pennebaker Inventory of Limbic Languidness) scores associated with lower surface area of the anterior cingulate cortex, a key hub of the salience
network. The salience network role is to choose relevant context-dependent stimuli from the environment or internally for the organism to direct its attention and resources to.85 The PILL questionnaire is conceptualized as a measure the propensity of an individual to report physical symptoms and a measure of “somatic focus”.86,87 Females with obesity have been shown to have greater salience network connectivity88, and the neural signatures support the incentive salience model. The incentive salience model states the motivational value for food is based on the sight, smell and taste of ultra-processed foods, and reduces the incentive value for other rewards.89 The increased somatic focus and alterations in salience network hubs in females with high BMI further corroborate these past findings.
Paul Ian Cross | April 13, 2023
...The (MRI) analysis was able to correctly differentiate high BMI from normal BMI participants and males with high BMI from females with high BMI with 77% and 75% accuracy, respectively.
...(Dr. Arpana Gupta, associate professor at the David Geffen School of Medicine at UCLA and lead author of the study) noted that women with obesity exhibited changes in emotion-related brain regions that were linked to higher levels of compulsive eating. Meanwhile, in men, brain regions related to eating behavior and obesity were associated with gut and visceral sensations linked to abdominal discomfort and hunger...
https://www.medicalnewstoday.com/articles/obesity-men-and-women-have-different-d...
----------------------------------------------
Ravi R Bhatt et al. 2023. Integrated multimodal brain signatures predict sex-specific obesity status (Accepted Manuscript). Brain Communications Published: 04 April 2023 https://doi.org/10.1093/braincomms/fcad098 https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcad0...
Abstract
... models differentiated high BMI against non-obese BMI participants, and males with high BMI against females with high BMI obtaining balanced accuracies of 77% and 75% respectively. Sex-specific differences within the cortico-basal-ganglia-thalamic-cortico loop, the choroid plexus-cereberospinal fluid system, salience, sensorimotor and deafult-mode networks were identified, and were associated with early life adversity, mental health quality, and greater somatosensation. Results showed multi-modal brain signatures suggesting sex-specific cortical mechanisms underlying obesity, which fosters clinical implications for tailored obesity interventions based on sex.
Discussion
The objective of the study was to examine sex differences in brain networks related to obesity.
The main findings of the study were: 1) greater choroid plexus and ventricular and volume in high
BMI individuals was associated with anatomical connectivity alterations in the cortico-basal
ganglia-thalamo-cortical loop; 2) greater early life trauma was associated with greater volume and
surface area and anatomical connectivity of the anterior insula and greater sensorimotor-DMN
resting-state connectivity; 3) compared to males with high BMI, females with high BMI showed
lower mental health scores which was associated with lower amygdala resting-state functional
connectivity to the SMN; 4) and compared to males with high BMI, females with high BMI had
greater PILL scores which were associated with lower surface area and volume in the anterior
cingulate cortex. Our results provide a sex-specific biological marker that could explain the short-
term feeding regulation and sensory processing patterns seen in females with obesity. To our
knowledge, this is the first study to utilize a data-driven approach to predict the sex-specific obesity
status of an individual based on multimodal brain signatures.
BMI-Dependent Effects on Brain
Individuals with high BMI displayed lower connectivity within the cortico-basal-ganglia-thalamo-cortico (CBGTC) loop which was associated with greater bilateral lateral ventricle volume. The CBGTC loop plays a key role in the reward circuitry, and in the context of obesity is known to receive dopaminergic input from the ventral tegmental area and substantia nigra to regulate motivational and incentive properties of food.66 Altered white matter properties in this
loop have been shown repeatedly,67 and lower count of white matter tracts within this circuitry can translate to the individual being less efficiently being able to regulate food intake beyond hemostatic needs. Our results showed changes in many regions of the brain which respond to food or food-associated cues66 and were highly correlated with early life trauma... ... In the context of obesity, those with early life trauma may suggest a risk factor for a consistently active threat response, as observed in individuals with obesity indexed via psychophysiological
parameters.69
The current results show greater choroid plexus and ventricle volume in those with high BMI. ... insulin is produced by ependymal cells of the choroid plexus ...dense expression of leptin receptors in the choroid plexus71 and its role in transporting leptin into the brain across the blood brain barrier,72 suggests the current results of greater choroid plexus and ventricle volume may be directly reflective of the amount of adipose tissue in the body.73 Leptin and insulin are known to be very high in obese individuals due to the resistantance that develops over time. The body compensates by releasing more of these hormones,74,75 which has the potential to be reflected via larger choroid plexus and ventricular volumes...yhose with high BMI had greater anatomical connectivity between the vmPFC and anterior insula, along with greater surface area of the anterior insula, where much of hedonic value processing is conducted.66 Moreover, the current results may suggest accelerated aging in those with high BMI, as greater ventricular volume in the context of aging has been associated with greater BMI...
Sex-Specific and-BMI Effects on Brain
Compared to males with high BMI, females with high BMI showed lower scores on the mental health subscale of the SF-12, which was highly correlated to lower resting-state connectivity between the amygdala and various regions of the sensorimotor network. These regions of the sensorimotor network also had greater mean curvature. Lower connectivity between the amygdala and sensorimotor network was associated with greater anxiety and lower resilience, both of which were observed in females with high BMI. Regions in the sensorimotor network, have been implicated in inappropriate cognitive evaluations of incoming sensory stimuli, resulting in an increased motivational reward placed on food-related stimuli, especially in females compared to males.79,80 ...Lower connectivity between the amygdala and this established sensorimotor network in women with high BMI compared to males suggests that females may have a reduced capacity to integrate emotions with action directed goal planning, resulting in greater “emotional overeating” compared to males.83,84 ... lower mental health scores in females with high BMI compared to males with high BMI.
Females with high BMI compared to males with high BMI also had greater PILL (Pennebaker Inventory of Limbic Languidness) scores associated with lower surface area of the anterior cingulate cortex, a key hub of the salience
network. The salience network role is to choose relevant context-dependent stimuli from the environment or internally for the organism to direct its attention and resources to.85 The PILL questionnaire is conceptualized as a measure the propensity of an individual to report physical symptoms and a measure of “somatic focus”.86,87 Females with obesity have been shown to have greater salience network connectivity88, and the neural signatures support the incentive salience model. The incentive salience model states the motivational value for food is based on the sight, smell and taste of ultra-processed foods, and reduces the incentive value for other rewards.89 The increased somatic focus and alterations in salience network hubs in females with high BMI further corroborate these past findings.
139margd
Microbiology: Gut microbiota may contribute to anorexia nervosa development
Nature Microbiology | April 18, 2023
Physiological and behavioural changes in people with anorexia nervosa may be associated with gut bacteria and their metabolites, and some of these associations can be demonstrated in a mouse model...
https://www.natureasia.com/en/research/highlight/14463
--------------------------------------------
Yong Fan et al. 2023. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice.
Nature Microbiology (17 April 2023) doi:10.1038/s41564-023-01355-5 https://www.nature.com/articles/s41564-023-01355-5
Nature Microbiology | April 18, 2023
Physiological and behavioural changes in people with anorexia nervosa may be associated with gut bacteria and their metabolites, and some of these associations can be demonstrated in a mouse model...
https://www.natureasia.com/en/research/highlight/14463
--------------------------------------------
Yong Fan et al. 2023. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice.
Nature Microbiology (17 April 2023) doi:10.1038/s41564-023-01355-5 https://www.nature.com/articles/s41564-023-01355-5
140margd
Weight loss associated w curcumin (turmeric extract) was not huge, though welcome, I'm sure. More impressive to me and my old doggie (16) is relief from morning stiffness (inflammation) with Super Bio-Curcumin Turmeric Extract (Life Extension): https://www.hopkinsmedicine.org/health/wellness-and-prevention/turmeric-benefits
Chanita Unhapipatpong et al. 2023. The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials. The American Journal of Clinical Nutrition, Volume 117, ISSUE 5, P1005-1016, 8 May 2023. DOI:https://doi.org/10.1016/j.ajcnut.2023.03.006 https://ajcn.nutrition.org/article/S0002-9165(23)46260-0/fulltext
Abstract
Background
Curcumin supplementation may promote weight loss and ameliorate obesity-related complications through its antioxidative and anti-inflammatory properties.
Objective
An umbrella review and updated meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effect of curcumin supplementation on anthropometric indices.
Methods
Systematic reviews and meta-analyses (SRMAs) of RCTs were identified from electronic databases (Medline, Scopus, Cochrane, and Google Scholar) up to 31 March, 2022, without language restriction. SRMAs were included if they assessed curcumin supplementation on any of the following: BMI, body weight (BW), or waist circumference (WC). Subgroup analyses were performed, stratifying by patient types, severity of obesity, and curcumin formula. The study protocol was a priori registered.
Results
From an umbrella review, 14 SRMAs with 39 individual RCTs were included with a high degree of overlap. In addition, searching was updated from the last search of included SRMAs in April 2021 up to 31 March, 2022, and we found 11 additional RCTs, bringing the total up to 50 RCTs included in the updated meta-analyses. Of these, 21 RCTs were deemed of high risk of bias. Curcumin supplementation significantly reduced BMI, BW, and WC with mean differences (MDs) of −0.24 kg/m2 ..., −0.59 kg ..., and −1.32 cm ..., respectively. The bioavailability-enhanced form reduced BMI, BWs, and WC more, with MDs of −0.26 kg/m2 ..., −0.80 kg ... and −1.41 cm ...), respectively. Significant effects were also seen in subgroups of patients, especially in adults with obesity and diabetes.
Conclusions
Curcumin supplementation significantly reduces anthropometric indices, and bioavailability-enhanced formulas are preferred. Augmenting curcumin supplement with lifestyle modification should be an option for weight reduction.
This trial was registered at PROSPERO as CRD42022321112 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321112).
Chanita Unhapipatpong et al. 2023. The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials. The American Journal of Clinical Nutrition, Volume 117, ISSUE 5, P1005-1016, 8 May 2023. DOI:https://doi.org/10.1016/j.ajcnut.2023.03.006 https://ajcn.nutrition.org/article/S0002-9165(23)46260-0/fulltext
Abstract
Background
Curcumin supplementation may promote weight loss and ameliorate obesity-related complications through its antioxidative and anti-inflammatory properties.
Objective
An umbrella review and updated meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effect of curcumin supplementation on anthropometric indices.
Methods
Systematic reviews and meta-analyses (SRMAs) of RCTs were identified from electronic databases (Medline, Scopus, Cochrane, and Google Scholar) up to 31 March, 2022, without language restriction. SRMAs were included if they assessed curcumin supplementation on any of the following: BMI, body weight (BW), or waist circumference (WC). Subgroup analyses were performed, stratifying by patient types, severity of obesity, and curcumin formula. The study protocol was a priori registered.
Results
From an umbrella review, 14 SRMAs with 39 individual RCTs were included with a high degree of overlap. In addition, searching was updated from the last search of included SRMAs in April 2021 up to 31 March, 2022, and we found 11 additional RCTs, bringing the total up to 50 RCTs included in the updated meta-analyses. Of these, 21 RCTs were deemed of high risk of bias. Curcumin supplementation significantly reduced BMI, BW, and WC with mean differences (MDs) of −0.24 kg/m2 ..., −0.59 kg ..., and −1.32 cm ..., respectively. The bioavailability-enhanced form reduced BMI, BWs, and WC more, with MDs of −0.26 kg/m2 ..., −0.80 kg ... and −1.41 cm ...), respectively. Significant effects were also seen in subgroups of patients, especially in adults with obesity and diabetes.
Conclusions
Curcumin supplementation significantly reduces anthropometric indices, and bioavailability-enhanced formulas are preferred. Augmenting curcumin supplement with lifestyle modification should be an option for weight reduction.
This trial was registered at PROSPERO as CRD42022321112 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321112).
141margd
"Older adults showed no significant increase in mortality between BMI of 22.5 and 34.9"??
'Overweight' BMI Not Tied to Higher Risk of Death, U.S. Data Suggest
— Though clear link seen for BMIs of 30 and above
Maja Clasen | July 7, 2023
...Of roughly half a million U.S. adults captured in the 1999-2018 surveys, a slightly lower risk for death over 9 years of median follow-up was observed among people with a BMI in the overweight range compared with a reference group within the normal range (BMI of 22.5-24.9):
BMI 25-27.4: adjusted HR 0.95 (95% CI 0.92-0.98)
BMI 27.5-29.9: adjusted HR 0.93 (95% CI 0.90-0.96)
...Compared with the reference group, BMIs in the obesity range (30 and above) were associated with a 21% to 108% increased mortality risk in further adjusted analyses that only included healthy never-smokers and omitted participants who died within 2 years of follow-up...
https://www.medpagetoday.com/primarycare/obesity/105368
--------------------------------------------------------------
Aayush Visaria and Soko Setoguchi 2023. Body mass index and all-cause mortality in a 21st century U.S. population: A National Health Interview Survey analysis. PLOS Published: July 5, 2023. https://doi.org/10.1371/journal.pone.0287218 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0287218
Abstract
...Results
The study sample included 554,332 adults (mean age 46 years..., 50% female, 69% non-Hispanic White). Over a median follow-up of 9 years (IQR 5–14) and maximum follow-up of 20 years, there were 75,807 deaths. The risk of all-cause mortality was similar across a wide range of BMI categories: compared to BMI of 22.5–24.9 kg/m2, the adjusted HR was 0.95... for BMI of 25.0–27.4 and 0.93 ...for BMI of 27.5–29.9. These results persisted after restriction to healthy never-smokers and exclusion of subjects who died within the first two years of follow-up. A 21–108% increased mortality risk was seen for BMI 30 or more. Older adults showed no significant increase in mortality between BMI of 22.5 and 34.9, while in younger adults this lack of increase was limited to the BMI range of 22.5 to 27.4.
Conclusion
The risk of all-cause mortality was elevated by 21–108% among participants with BMI ≥30. BMI may not necessarily increase mortality independently of other risk factors in adults, especially older adults, with overweight BMI. Further studies incorporating weight history, body composition, and morbidity outcomes are needed to fully characterize BMI-mortality associations.
...Discussion
...In conclusion, our findings suggest that BMI in the overweight range is generally not associated with increased risk of all-cause mortality. Our study suggests that BMI may not necessarily increase mortality independently of other risk factors in those with BMI of 25.0–29.9 and in older adults with BMI of 25.0–34.9. Consequently, this highlights the potential limitations of BMI in capturing true adiposity and limitations of its clinical value independent of traditional metabolic syndrome criteria. Longitudinal studies incorporating weight history, complementary measures of body composition and body fat distribution (e.g. waist circumference, waist-to-hip ratio), undermeasured consequences of weight (e.g. psychological toll of obesity...), and morbidity outcomes are needed to fully characterize the relationship between BMI and mortality.
'Overweight' BMI Not Tied to Higher Risk of Death, U.S. Data Suggest
— Though clear link seen for BMIs of 30 and above
Maja Clasen | July 7, 2023
...Of roughly half a million U.S. adults captured in the 1999-2018 surveys, a slightly lower risk for death over 9 years of median follow-up was observed among people with a BMI in the overweight range compared with a reference group within the normal range (BMI of 22.5-24.9):
BMI 25-27.4: adjusted HR 0.95 (95% CI 0.92-0.98)
BMI 27.5-29.9: adjusted HR 0.93 (95% CI 0.90-0.96)
...Compared with the reference group, BMIs in the obesity range (30 and above) were associated with a 21% to 108% increased mortality risk in further adjusted analyses that only included healthy never-smokers and omitted participants who died within 2 years of follow-up...
https://www.medpagetoday.com/primarycare/obesity/105368
--------------------------------------------------------------
Aayush Visaria and Soko Setoguchi 2023. Body mass index and all-cause mortality in a 21st century U.S. population: A National Health Interview Survey analysis. PLOS Published: July 5, 2023. https://doi.org/10.1371/journal.pone.0287218 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0287218
Abstract
...Results
The study sample included 554,332 adults (mean age 46 years..., 50% female, 69% non-Hispanic White). Over a median follow-up of 9 years (IQR 5–14) and maximum follow-up of 20 years, there were 75,807 deaths. The risk of all-cause mortality was similar across a wide range of BMI categories: compared to BMI of 22.5–24.9 kg/m2, the adjusted HR was 0.95... for BMI of 25.0–27.4 and 0.93 ...for BMI of 27.5–29.9. These results persisted after restriction to healthy never-smokers and exclusion of subjects who died within the first two years of follow-up. A 21–108% increased mortality risk was seen for BMI 30 or more. Older adults showed no significant increase in mortality between BMI of 22.5 and 34.9, while in younger adults this lack of increase was limited to the BMI range of 22.5 to 27.4.
Conclusion
The risk of all-cause mortality was elevated by 21–108% among participants with BMI ≥30. BMI may not necessarily increase mortality independently of other risk factors in adults, especially older adults, with overweight BMI. Further studies incorporating weight history, body composition, and morbidity outcomes are needed to fully characterize BMI-mortality associations.
...Discussion
...In conclusion, our findings suggest that BMI in the overweight range is generally not associated with increased risk of all-cause mortality. Our study suggests that BMI may not necessarily increase mortality independently of other risk factors in those with BMI of 25.0–29.9 and in older adults with BMI of 25.0–34.9. Consequently, this highlights the potential limitations of BMI in capturing true adiposity and limitations of its clinical value independent of traditional metabolic syndrome criteria. Longitudinal studies incorporating weight history, complementary measures of body composition and body fat distribution (e.g. waist circumference, waist-to-hip ratio), undermeasured consequences of weight (e.g. psychological toll of obesity...), and morbidity outcomes are needed to fully characterize the relationship between BMI and mortality.
142margd
Science Magazine @ScienceMagazine | 3:30 PM · Aug 3, 2023:
A new #ScienceEditorial by @cbulik and hardawayja examines the recent advances—and potential risks—in medical treatments for obesity and weight loss.
"… effective obesity treatments exist for the first time." -
Cynthia M. Bulik and J. Andrew Hardaway 2023. Turning the tide on obesity? (Editorial) Science 3 Aug 2023 Vol 381, Issue 6657 p. 463 DOI: 10.1126/science.adj9953 https://scim.ag/3Bd https://www.science.org/doi/10.1126/science.adj9953
A new #ScienceEditorial by @cbulik and hardawayja examines the recent advances—and potential risks—in medical treatments for obesity and weight loss.
"… effective obesity treatments exist for the first time." -
Cynthia M. Bulik and J. Andrew Hardaway 2023. Turning the tide on obesity? (Editorial) Science 3 Aug 2023 Vol 381, Issue 6657 p. 463 DOI: 10.1126/science.adj9953 https://scim.ag/3Bd https://www.science.org/doi/10.1126/science.adj9953
143margd
Fructose survival theory makes sense in that bears preparing for hibernation eat fruit and berries, which would be in season. But we evolved eating fruit (we see color red, lost ability to make vitamin C), so effect would be less in us?
How does fructose intake contribute to obesity?
Katharine Lang | August 7, 2023
The study proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biological response (survival switch) that aims to protect animals before a crisis, such as hibernation.
...unlike glucose which is used as immediate fuel, fructose triggers the body to store fuel.
So, how does fructose induce the body to store energy rather than use it?
Usually, adenosine triphosphate (ATP), the molecule that provides energy to power all cell processes, is used and rapidly replaced from nutrient intake or fat stores.
However, fructose lowers ATP concentration in cells and reduces the ability to make more ATP.
When ATP levels drop enough, this sets off a series of chemical reactions that stop the mitochondria of the cell from producing more ATP, and causes them oxidative stress.
As well as causing ATP levels to drop, ingestion of fructose stimulates further food intake. These extra calories are then stored as fat. Eventually, the ATP levels increase again, but the stored fat remains.
Over time, repeated oxidative stress leads to permanent mitochondrial dysfunction. In a hibernating mammal, the body adapts to the low ATP levels by reducing the resting metabolic rate.
...Although fructose is the natural sugar that makes fruit sweet, a typical Western diet contains many other sources of fructose.
The majority comes from table sugar, sucrose — a molecule made up of glucose and fructose chemically bonded together — and high fructose corn syrup (HFCS), a sweetener made from cornstarch...
https://www.medicalnewstoday.com/articles/how-does-fructose-intake-contribute-to...
-----------------------------------------
Richard J. Johnson et al. 2023. The fructose survival hypothesis for obesity. Philosophical Transactions of the Royal Society B Biological Sciences, 11 September 2023,
Volume 378 Issue 1885. https://doi.org/10.1098/rstb.2022.0230 https://royalsocietypublishing.org/doi/10.1098/rstb.2022.0230#d1e1566
Abstract
The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animals in advance of crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of ‘thrifty genes’ coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span.
How does fructose intake contribute to obesity?
Katharine Lang | August 7, 2023
The study proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biological response (survival switch) that aims to protect animals before a crisis, such as hibernation.
...unlike glucose which is used as immediate fuel, fructose triggers the body to store fuel.
So, how does fructose induce the body to store energy rather than use it?
Usually, adenosine triphosphate (ATP), the molecule that provides energy to power all cell processes, is used and rapidly replaced from nutrient intake or fat stores.
However, fructose lowers ATP concentration in cells and reduces the ability to make more ATP.
When ATP levels drop enough, this sets off a series of chemical reactions that stop the mitochondria of the cell from producing more ATP, and causes them oxidative stress.
As well as causing ATP levels to drop, ingestion of fructose stimulates further food intake. These extra calories are then stored as fat. Eventually, the ATP levels increase again, but the stored fat remains.
Over time, repeated oxidative stress leads to permanent mitochondrial dysfunction. In a hibernating mammal, the body adapts to the low ATP levels by reducing the resting metabolic rate.
...Although fructose is the natural sugar that makes fruit sweet, a typical Western diet contains many other sources of fructose.
The majority comes from table sugar, sucrose — a molecule made up of glucose and fructose chemically bonded together — and high fructose corn syrup (HFCS), a sweetener made from cornstarch...
https://www.medicalnewstoday.com/articles/how-does-fructose-intake-contribute-to...
-----------------------------------------
Richard J. Johnson et al. 2023. The fructose survival hypothesis for obesity. Philosophical Transactions of the Royal Society B Biological Sciences, 11 September 2023,
Volume 378 Issue 1885. https://doi.org/10.1098/rstb.2022.0230 https://royalsocietypublishing.org/doi/10.1098/rstb.2022.0230#d1e1566
Abstract
The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animals in advance of crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of ‘thrifty genes’ coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span.
144margd
The green tea effect: From gut microbes to weight loss, new insights emerge
Vijay Kumar Malesu | Aug 8 2023
...Conclusions
The researchers found a unique pattern in gut microbiota clustering in mice fed a HF (high fat) diet supplemented with a green tea. This infusion, particularly at a 4% concentration, substantially improved the intestinal microflora of obese mice, mitigating the metabolic alterations caused by the HF diet.
The study identified 32 genera, including Akkermansia, Saccharofermentans, Acetatifactor, Bacteroides, Alistipes, Allobaculum, and Falsiporphyromonas, as biomarkers associated with the HF diet.
Of these, TPP (total tea polyphenols) notably enhanced the presence of Akkermansia, playing a vital role in re-establishing a healthy bacterial community necessary for countering obesity.
Thus, the research suggests that green tea can be a potent remedy for HF diet-induced complications, primarily by modifying gut microbial communities.
Journal reference:
Mei, H. et al. (2023) "The Role of Green Tea on the Regulation of Gut Microbes and Prevention of High-Fat Diet-Induced Metabolic Syndrome in Mice", Foods, 12(15), p. 2953. doi: 10.3390/foods12152953. https://www.mdpi.com/2304-8158/12/15/2953
https://www.news-medical.net/news/20230808/The-green-tea-effect-From-gut-microbe...
Vijay Kumar Malesu | Aug 8 2023
...Conclusions
The researchers found a unique pattern in gut microbiota clustering in mice fed a HF (high fat) diet supplemented with a green tea. This infusion, particularly at a 4% concentration, substantially improved the intestinal microflora of obese mice, mitigating the metabolic alterations caused by the HF diet.
The study identified 32 genera, including Akkermansia, Saccharofermentans, Acetatifactor, Bacteroides, Alistipes, Allobaculum, and Falsiporphyromonas, as biomarkers associated with the HF diet.
Of these, TPP (total tea polyphenols) notably enhanced the presence of Akkermansia, playing a vital role in re-establishing a healthy bacterial community necessary for countering obesity.
Thus, the research suggests that green tea can be a potent remedy for HF diet-induced complications, primarily by modifying gut microbial communities.
Journal reference:
Mei, H. et al. (2023) "The Role of Green Tea on the Regulation of Gut Microbes and Prevention of High-Fat Diet-Induced Metabolic Syndrome in Mice", Foods, 12(15), p. 2953. doi: 10.3390/foods12152953. https://www.mdpi.com/2304-8158/12/15/2953
https://www.news-medical.net/news/20230808/The-green-tea-effect-From-gut-microbe...
145margd
John R. Speakman et al. 2023. Unanswered questions about the causes of obesity
Obesity is now a global pandemic, but there is little consensus about the causes
Science, 31 Aug 2023. Vol 381, Issue 6661, pp. 944-946
DOI: 10.1126/science.adg2718 https://www.science.org/doi/10.1126/science.adg2718
...Confusion about the causes of obesity has arisen based on the false dichotomy of genes versus environment (rather than the combined effects of genes and environment). At any point in time, most of the variance in levels of obesity among individuals may be genetic. But, changes across time are predominantly driven by the environment. Which individuals deposit the most fat in response to environmental change is influenced by both...
Obesity is now a global pandemic, but there is little consensus about the causes
Science, 31 Aug 2023. Vol 381, Issue 6661, pp. 944-946
DOI: 10.1126/science.adg2718 https://www.science.org/doi/10.1126/science.adg2718
...Confusion about the causes of obesity has arisen based on the false dichotomy of genes versus environment (rather than the combined effects of genes and environment). At any point in time, most of the variance in levels of obesity among individuals may be genetic. But, changes across time are predominantly driven by the environment. Which individuals deposit the most fat in response to environmental change is influenced by both...
146margd
Protein’s Pull: The Dietary Dynamics Driving Obesity
University of Sydney | September 4, 2023
...Humans, like many other species, regulate protein intake more strongly than any other dietary component and so if protein is diluted there is a compensatory increase in food intake. The hypothesis proposes that the dilution of protein in modern-day diets by fat and carbohydrate-rich processed foods is driving increased energy intake as the body seeks to satisfy its natural protein drive — eating unnecessary calories until it does so.
...Because data indicate that children and adolescents also show protein leverage, the authors discuss the potential impact of exposure to a high-protein diet in preconception or early life (for example through some infant formula feeds) in potentially setting up increased protein requirements and greater susceptibility to lower protein, processed diets in later years.
...The authors conclude: “…it is only through situating specific nutrients and biological factors within their broader context that we can hope to identify sustainable intervention points for slowing and reversing the incidence of obesity and associated complications.”
https://scitechdaily.com/proteins-pull-the-dietary-dynamics-driving-obesity
---------------------------------------------------------
David Raubenheimer and Stephen J Simpson 2023. Protein appetite as an integrator in the obesity system: the protein leverage hypothesis. Philos Trans R Soc Lond B Biol Sci. 2023 Oct 23;378(1888):20220212.
doi: 10.1098/rstb.2022.0212. Epub 2023 Sep 4. https://pubmed.ncbi.nlm.nih.gov/37661737/
Abstract
Despite the large volume and extensive range of obesity research, there is substantial disagreement on the causes and effective preventative strategies. We suggest the field will benefit from greater emphasis on integrative approaches that examine how various potential contributors interact, rather than regarding them as competing explanations. We demonstrate the application of nutritional geometry, a multi-nutrient integrative framework developed in the ecological sciences, to obesity research. Such studies have shown that humans, like many other species, regulate protein intake more strongly than other dietary components, and consequently if dietary protein is diluted there is a compensatory increase in food intake-a process called protein leverage. The protein leverage hypothesis (PLH) proposes that the dilution of protein in modern food supplies by fat and carbohydrate-rich highly processed foods has resulted in increased energy intake through protein leverage. We present evidence for the PLH from a variety of sources (mechanistic, experimental and observational), and show that this mechanism is compatible with many other findings and theories in obesity research. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.*
* https://royalsociety.org/science-events-and-lectures/2022/10/causes-obesity/
University of Sydney | September 4, 2023
...Humans, like many other species, regulate protein intake more strongly than any other dietary component and so if protein is diluted there is a compensatory increase in food intake. The hypothesis proposes that the dilution of protein in modern-day diets by fat and carbohydrate-rich processed foods is driving increased energy intake as the body seeks to satisfy its natural protein drive — eating unnecessary calories until it does so.
...Because data indicate that children and adolescents also show protein leverage, the authors discuss the potential impact of exposure to a high-protein diet in preconception or early life (for example through some infant formula feeds) in potentially setting up increased protein requirements and greater susceptibility to lower protein, processed diets in later years.
...The authors conclude: “…it is only through situating specific nutrients and biological factors within their broader context that we can hope to identify sustainable intervention points for slowing and reversing the incidence of obesity and associated complications.”
https://scitechdaily.com/proteins-pull-the-dietary-dynamics-driving-obesity
---------------------------------------------------------
David Raubenheimer and Stephen J Simpson 2023. Protein appetite as an integrator in the obesity system: the protein leverage hypothesis. Philos Trans R Soc Lond B Biol Sci. 2023 Oct 23;378(1888):20220212.
doi: 10.1098/rstb.2022.0212. Epub 2023 Sep 4. https://pubmed.ncbi.nlm.nih.gov/37661737/
Abstract
Despite the large volume and extensive range of obesity research, there is substantial disagreement on the causes and effective preventative strategies. We suggest the field will benefit from greater emphasis on integrative approaches that examine how various potential contributors interact, rather than regarding them as competing explanations. We demonstrate the application of nutritional geometry, a multi-nutrient integrative framework developed in the ecological sciences, to obesity research. Such studies have shown that humans, like many other species, regulate protein intake more strongly than other dietary components, and consequently if dietary protein is diluted there is a compensatory increase in food intake-a process called protein leverage. The protein leverage hypothesis (PLH) proposes that the dilution of protein in modern food supplies by fat and carbohydrate-rich highly processed foods has resulted in increased energy intake through protein leverage. We present evidence for the PLH from a variety of sources (mechanistic, experimental and observational), and show that this mechanism is compatible with many other findings and theories in obesity research. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.*
* https://royalsociety.org/science-events-and-lectures/2022/10/causes-obesity/
147margd
Eric Robinson 2023. Veganism and body weight: An N of 1 self-experiment (Brief communication). Physiology & Behavior
Volume 270, 15 October 2023, 114301. https://doi.org/10.1016/j.physbeh.2023.114301 https://www.sciencedirect.com/science/article/pii/S0031938423002263
Abstract
The causal effect that veganism has on body weight has not been scientifically examined. An N of 1 self-experiment was conducted in which blinded body weight and additional behavioural and psychological measures were assessed during two phases of vegan vs. non-vegan lifestyle adherence. In study phase 1, body weight change was -0.8 kg over 1 month of veganism (vs. +0.5 kg non-vegan month). In study phase 2, weight change was -1.2 kg over two veganism months (vs. +1.6 kg non-vegan months). Behavioural and psychological measures were similar during vegan vs. non-vegan periods. Veganism appeared to reduce body weight in this N of 1 self-experiment.
Volume 270, 15 October 2023, 114301. https://doi.org/10.1016/j.physbeh.2023.114301 https://www.sciencedirect.com/science/article/pii/S0031938423002263
Abstract
The causal effect that veganism has on body weight has not been scientifically examined. An N of 1 self-experiment was conducted in which blinded body weight and additional behavioural and psychological measures were assessed during two phases of vegan vs. non-vegan lifestyle adherence. In study phase 1, body weight change was -0.8 kg over 1 month of veganism (vs. +0.5 kg non-vegan month). In study phase 2, weight change was -1.2 kg over two veganism months (vs. +1.6 kg non-vegan months). Behavioural and psychological measures were similar during vegan vs. non-vegan periods. Veganism appeared to reduce body weight in this N of 1 self-experiment.
149margd
>148 pnppl: "An average difference of 302kcals per day was estimated to fully account for difference in body weight trajectories between vegan vs. non-vegan study periods", but looking more closely, you're right--it is a little bizarre!
:D
:D
150margd
How might carb and fat consumption affect longevity in men vs women?
Robby Berman | September 10, 2023
...The study finds that men who eat too few carbohydrates daily may increase their risk of dying, while women who consume insufficient quantities of fat may do the same.
The researchers studied people in Japan, so the findings may or may not apply as well to Western populations...
https://www.medicalnewstoday.com/articles/how-does-carb-and-fat-consumption-affe...
-------------------------------------------------------------
Takashi Tamura et al. 2023. Dietary Carbohydrate and Fat Intakes and Risk of Mortality in the Japanese Population: the Japan Multi-Institutional Collaborative Cohort Study. The Journal of Nutrition
Volume 153, Issue 8, August 2023, Pages 2352-2368. https://www.sciencedirect.com/science/article/abs/pii/S0022316623721986
Abstract
...Results. During a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to leass than 55% of energy from carbohydrate, those who consumed less than 40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59...). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR ... was 1.71... for 65% or more of energy from carbohydrate compared with that for 50% to less than 55%... Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR... for 35% or more was 1.79 ... compared with that for 20% to less than 25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively).
Conclusions
An unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake.
Robby Berman | September 10, 2023
...The study finds that men who eat too few carbohydrates daily may increase their risk of dying, while women who consume insufficient quantities of fat may do the same.
The researchers studied people in Japan, so the findings may or may not apply as well to Western populations...
https://www.medicalnewstoday.com/articles/how-does-carb-and-fat-consumption-affe...
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Takashi Tamura et al. 2023. Dietary Carbohydrate and Fat Intakes and Risk of Mortality in the Japanese Population: the Japan Multi-Institutional Collaborative Cohort Study. The Journal of Nutrition
Volume 153, Issue 8, August 2023, Pages 2352-2368. https://www.sciencedirect.com/science/article/abs/pii/S0022316623721986
Abstract
...Results. During a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to leass than 55% of energy from carbohydrate, those who consumed less than 40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59...). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR ... was 1.71... for 65% or more of energy from carbohydrate compared with that for 50% to less than 55%... Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR... for 35% or more was 1.79 ... compared with that for 20% to less than 25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively).
Conclusions
An unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake.
151margd
Maintaining a Vegetarian Diet Might Be in Your Genes
Sarah Kuta | October 6, 2023
...three genes were significantly more common among the vegetarians. Two of those variants—called NPC1 and RMC—are involved in fat metabolism and brain function. The third, RIOK3, plays a variety of roles in the body, including supporting the immune system.
On top of those three, the team found another 31 genes they say could potentially be associated with vegetarianism.
The scientists are still teasing out exactly what these correlations might mean. But they suspect some people lacking these genes may need to eat meat to get certain fatty lipids, while the bodies of people with these genes may be able to produce the lipids internally.
...Past research has found other links between genetics and diet, including whether people like black coffee or grapes and orange juice. Genes may also be responsible for why some people love cilantro, while others think it tastes like soap...
https://www.smithsonianmag.com/smart-news/maintaining-a-vegetarian-diet-might-be...
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Nabeel R. Yaseen et al. 2023. Genetics of vegetarianism: A genome-wide association study. PLOS Published: October 4, 2023. https://doi.org/10.1371/journal.pone.0291305 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291305
Sarah Kuta | October 6, 2023
...three genes were significantly more common among the vegetarians. Two of those variants—called NPC1 and RMC—are involved in fat metabolism and brain function. The third, RIOK3, plays a variety of roles in the body, including supporting the immune system.
On top of those three, the team found another 31 genes they say could potentially be associated with vegetarianism.
The scientists are still teasing out exactly what these correlations might mean. But they suspect some people lacking these genes may need to eat meat to get certain fatty lipids, while the bodies of people with these genes may be able to produce the lipids internally.
...Past research has found other links between genetics and diet, including whether people like black coffee or grapes and orange juice. Genes may also be responsible for why some people love cilantro, while others think it tastes like soap...
https://www.smithsonianmag.com/smart-news/maintaining-a-vegetarian-diet-might-be...
---------------------------------------------------------
Nabeel R. Yaseen et al. 2023. Genetics of vegetarianism: A genome-wide association study. PLOS Published: October 4, 2023. https://doi.org/10.1371/journal.pone.0291305 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291305
152margd
Smoking-Related Metabolic Changes Partly Drive Type 2 Diabetes Risk
— Those with the most metabolic changes, genetic risk had a threefold higher diabetes risk
Kristen Monaco | October 6, 2023
https://www.medpagetoday.com/meetingcoverage/easd/106681
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Wei Y, et al "Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility" European Association for the Study of Diabetes EASD 2023; Poster 322. https://www.easd.org/annual-meeting/easd-2023.html
— Those with the most metabolic changes, genetic risk had a threefold higher diabetes risk
Kristen Monaco | October 6, 2023
https://www.medpagetoday.com/meetingcoverage/easd/106681
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Wei Y, et al "Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility" European Association for the Study of Diabetes EASD 2023; Poster 322. https://www.easd.org/annual-meeting/easd-2023.html
153margd
Scientists Shed New Light on the Protein Diet Paradox
eLife | October 20, 2023
...“We know that many people deliberately consuming high-protein diets or consuming protein supplements to support their exercise regimen are not metabolically unhealthy, despite the body of evidence showing that high-protein levels can have detrimental metabolic effects,” says senior author Dudley Lamming, Associate Professor of Medicine (Endocrinology) at the Department of Medicine, School of Medicine and Public Health, University of Wisconsin. “Our research may explain this conundrum, by showing that resistance exercise protects from high-protein-induced fat gain in mice. This suggests that metabolically unhealthy, sedentary individuals with a high-protein diet or protein supplements might benefit from either reducing their protein intake or more resistance exercise.”
https://scitechdaily.com/scientists-shed-new-light-on-the-protein-diet-paradox/
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Michaela E. Trautman et al. 2023. Resistance exercise protects mice from protein-induced fat accretion. eLife. 16 October 2023. DOI: 10.7554/eLife.91007.1 https://elifesciences.org/reviewed-preprints/91007v1
Preprint
Abstract
...We find that despite having lower food consumption than the LP (low protein) group, HP (high protein) -fed mice gain significantly more fat mass than LP-fed mice when not exercising, while weight pulling protected HP-fed mice from this excess fat accretion. The HP diet augmented exercise-induced hypertrophy of the forearm flexor complex, and weight pulling ability increased more rapidly in the exercised HP-fed mice. Surprisingly, exercise did not protect from HP-induced changes in glycemic control. Our results confirm that HP diets can augment muscle hypertrophy and accelerate strength gain induced by resistance exercise without negative effects on fat mass, and also demonstrate that LP diets may be advantageous in the sedentary. Our results highlight the need to consider both dietary composition and activity, not simply calories, when taking a precision nutrition approach to health.
eLife | October 20, 2023
...“We know that many people deliberately consuming high-protein diets or consuming protein supplements to support their exercise regimen are not metabolically unhealthy, despite the body of evidence showing that high-protein levels can have detrimental metabolic effects,” says senior author Dudley Lamming, Associate Professor of Medicine (Endocrinology) at the Department of Medicine, School of Medicine and Public Health, University of Wisconsin. “Our research may explain this conundrum, by showing that resistance exercise protects from high-protein-induced fat gain in mice. This suggests that metabolically unhealthy, sedentary individuals with a high-protein diet or protein supplements might benefit from either reducing their protein intake or more resistance exercise.”
https://scitechdaily.com/scientists-shed-new-light-on-the-protein-diet-paradox/
-----------------------------------
Michaela E. Trautman et al. 2023. Resistance exercise protects mice from protein-induced fat accretion. eLife. 16 October 2023. DOI: 10.7554/eLife.91007.1 https://elifesciences.org/reviewed-preprints/91007v1
Preprint
Abstract
...We find that despite having lower food consumption than the LP (low protein) group, HP (high protein) -fed mice gain significantly more fat mass than LP-fed mice when not exercising, while weight pulling protected HP-fed mice from this excess fat accretion. The HP diet augmented exercise-induced hypertrophy of the forearm flexor complex, and weight pulling ability increased more rapidly in the exercised HP-fed mice. Surprisingly, exercise did not protect from HP-induced changes in glycemic control. Our results confirm that HP diets can augment muscle hypertrophy and accelerate strength gain induced by resistance exercise without negative effects on fat mass, and also demonstrate that LP diets may be advantageous in the sedentary. Our results highlight the need to consider both dietary composition and activity, not simply calories, when taking a precision nutrition approach to health.
En/na "Too Fat" Part Four!... ha continuat aquest tema.
