Newsletter #165

Newsletter #165: New Insights into Obesity and Appetite 🤔

Good morning, and of course happy Fourth of July weekend to all of our friends here in the US! 🎉

This week, we revisited some of the complicated science of body mass and appetite regulation.

Key takeaways:

🔹 People with obesity whose metabolic profiles appear mostly healthy remain at increased risk of disease;

🔹 The obesity-promoting effect of the FTO risk variants may be reduced by physical exercise;

🔹 The gastrointestinal hormone secretin may play a role in appetite regulation.

To get all the details, scroll on down 👇

This Week’s Research Highlights

📈 Having a mostly normal metabolic profile does not eliminate the risks associated with obesity.

Researchers at the University of Glasgow analyzed data from a large UK cohort (n = 381363) who were followed for a median of 11.2 years. They divided subjects based on whether or not they had obesity, and then further separated them based on whether they met the classification of “metabolically healthy obesity,” meaning having a BMI of at least 30 and at least four of six metabolically healthy criteria (refer to this podcast with Spencer Nadolsky to find out why this itself is problematic). Compared to metabolically healthy participants without obesity, participants with metabolically healthy obesity were 4.3 times more likely to have type 2 diabetes, 18% more likely to suffer heart attack or stroke, had a 76% higher risk of heart failure, were 28% more likely to suffer respiratory disease, and 19% more likely to suffer COPD. Importantly, it is also very likely that what we refer to as metabolically healthy obesity is in fact a transient state. The researchers found that, amongst a subset of participants with follow-up data, one-third of those with metabolically healthy obesity at the beginning of the study period became metabolically unhealthy within 3 to 5 years.

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Summary: Participants with metabolically healthy obesity were still more likely to have type 2 diabetes, heart attack or stroke, heart failure, respiratory disease, and COPD compared to metabolically healthy participants without obesity. The study also suggests that metabolically healthy obesity is likely a transient state, with one-third of participants becoming metabolically unhealthy within 3 to 5 years.

🧠 Secretin activates brown fat and induces satiation.

Researchers administered secretin intravenously in healthy, normal-weight male subjects, and measured the effects of the intervention on brown adipose tissue metabolism (via PET scan) and appetite (via fMRI). They found that secretin infusion increased brown fat glucose uptake by 57%, compared to placebo, which was accompanied by a 2% increase in whole body energy expenditure. Furthermore, secretin diminished activity in brain reward circuits when the men were shown appetizing food. This is the first study to demonstrate the presence of secretin receptors in brown adipose tissue, and that it is relevant to appetite regulation in humans. Maybe this discovery could point to useful treatments in the future?

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Summary: The study found that secretin infusion increased brown fat glucose uptake and energy expenditure, while also diminishing activity in brain reward circuits when shown appetizing food. This is the first study to demonstrate the presence of secretin receptors in brown adipose tissue, which could lead to useful treatments in the future.

🧬 Intense exercise may reduce the impact of FTO variants on obesity risk by decreasing FTO mRNA expression.

The FTO gene holds the strongest known association to obesity risk. However, some studies have suggested that its effects may be modulated by environmental and lifestyle factors. Researchers performed a meta-analysis of genetic data from 45 studies of adults (n = 218166), which also provided information on whether or not participants were physically active. They found that the association of the FTO risk allele with odds of obesity was reduced by 27% in adults who were physically active. A more recent trial shed some light on why this might be the case. A team of scientists recruited 28 untrained subjects and had them exercise on a stationary bike on two separate occasions at high intensity (80% of VO2peak) and low intensity (40% of VO2peak). Muscle biopsies from their legs revealed that FTO mRNA expression was significantly decreased after high intensity exercise. This may be through activation of AMPK, which has previously been shown to lower expression of FTO.

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Summary: This meta-analysis of genetic data from 45 studies of adults found that the association of the FTO risk allele with odds of obesity was reduced by 27% in adults who were physically active. A recent trial also found that FTO mRNA expression was significantly decreased after high intensity exercise, possibly through activation of AMPK.

Random Trivia Question of the Week

🤔 How big is the largest known ant colony in the world?

🐜 Answer

Podcasts We Loved This Week

Alan Flanagan & Danny Lennon: Is there a body weight setpoint? Models of body mass regulation. Via Sigma Nutrition Radio.

Spencer Nadolsky: Obesity and chronic disease risk. Via Sigma Nutrition Radio.

Products We Are Enjoying

Cronometer

You don’t have to track your food, but it is probably the surest and more efficient way to optimize your nutrition, especially if you have specific goals like losing weight. There are a lot of tracking apps out there but Cronometer is probably the most comprehensive one around, with the ability to track up to 82 micronutrients.

It is free and very easy to use - you can even scan food labels with the barcode scanner and add custom foods and recipes. Strongly recommended for health geeks who enjoy data.

humanOS Catalog Feature of the Week

Have a happy and safe July Fourth, and we'll see y'all next week, same time and place!

https://mailchi.mp/humanos.me/newsletter-165