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A Thermostat for Your Body Fat

Stephan J. Guyenet and Dr. Buck Joffrey discuss the science of body fat regulation

In this episode of Longevity Roadmap, host Dr. Buck Joffrey talks with neuroscientist Dr. Stephan J. Guyenet, author of The Hungry Brain, about the science behind body fat regulation. Dr. Guyenet explains how the brain, particularly the hypothalamus, plays a central role in controlling fat storage through a system he calls the “lipostat”—a kind of internal thermostat that regulates body fat.

Key Points:

The brain acts like a thermostat for body fat, triggering powerful defences—like increased hunger and reduced metabolism—when we try to lose weight, making long-term weight loss difficult. Leptin, a hormone released by fat tissue, helps the brain monitor and regulate body fat levels, but modern lifestyles, including poor diet, stress, and lack of sleep, can disrupt this system and lead to weight gain.

  • The Brain’s Lipostat Controls Body Fat: The hypothalamus acts like a thermostat for fat levels using hormones like leptin. Leptin, secreted by fat tissue, signals the brain to regulate hunger and energy use based on fat stores.
  • Leptin Resistance Fuels Weight Gain: Many people with obesity develop leptin resistance—where the brain becomes less responsive to leptin signals, raising the body's defended fat set point and making weight loss harder.
  • Evolution Didn’t Prepare Us for Abundance: Historically, humans faced food scarcity, not overabundance. As a result, our lipostat evolved to prevent starvation, not obesity—making it easier to gain weight than lose it.
  • Obesity Is More About the Brain than Insulin: Dr. Guyenet challenges the popular insulin-centric model of obesity, pointing instead to genetics and brain regulation as primary factors influencing body fatness.
  • Non-Hunger Eating Drives Overconsumption: Many overeating behaviours (e.g. stress, boredom, cravings) stem from non-homeostatic brain systems unrelated to actual energy needs, pushing us to consume more in modern environments.

Visit website: https://www.youtube.com/watch?v=Zl2w11MWcUU

See also

Longevity Roadmap Podcast

Podcast on science-backed strategies to slow aging and boost health with Buck Joffrey

Details last updated 26-Jun-2025

Mentioned in this Resource

Stephan Guyenet

Neuroscientist and obesity researcher