Genetics & Neurobiology of Obesity: Hypothalamus, Leptin, Gut Hormones, Weight Loss Drugs | Giles Yeo | 222

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Short Summary: The science of obesity and appetite regulation, blending genetics and neurobiology with practical insights

About the guest: Giles Yeo, PhD is a professor of molecular neuroendocrinology at the University of Cambridge. He leads a lab studying obesity and appetite regulation.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Nick interviews Dr. Giles Yeo about the genetics and neurobiology of obesity, starting with the discovery of leptin in the obese mouse model, detailing its role in appetite regulation via the hypothalamus, and discussing GLP-1 drugs like Ozempic for weight loss. It delves into how genetic factors, like the leptin-melanocortin pathway, influence hunger, the heritability of body weight, and societal factors driving the obesity epidemic, emphasizing the interplay of biology and environment.

Key Takeaways:

• Leptin, discovered through the obese mouse, signals fat levels to the brain, but its absence causes severe obesity and infertility, as seen in rare human mutations.
• The hypothalamus, a key brain region, senses hormones like leptin and GLP-1, balancing hunger and satiety through POMC (anorexigenic) and AgRP (orexigenic) neurons.
• Body weight heritability is 40-70% at the population level, but this does not mean that 40-70% of someone’s body fat composition is due to genetic factors outside human control. Dr. Yeo unpacks how to think about it.
• GLP-1 drugs (e.g., Ozempic) mimic gut hormones to reduce appetite, offering some people 15-25% weight loss, but require long-term safety monitoring.
• According to Dr. Yeo, obesity reflects energy imbalance, but nutritional density matters more than calorie counting for health, and societal changes are needed to prevent it.

Related episode:

• M&M #132: Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & Feeding Behavior | John Speakman

*Not medical advice.

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