Podcast Notes Playlist: Latest Episodes

#212 - The neuroscience of obesity | Stephan Guyenet, Ph.D.


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Podcast Notes Key Takeaways
  • “More than half of U.S. adults will be classified as actually having obesity at some point in their life if the current context is maintained. You see the same thing with type 2 diabetes.” – Dr. Stephan Guyenet
  • There is no demographic in the U.S. adults where we have not gotten much fatter over the last few decades – regardless of income, education, or geography – we’re getting fatter than we were
  • Obesity is highly heritable (about 75%) and preserved
  • Differences in body fatness between individuals are primarily determined by differences in how the brain is constructed and operates
  • Any time you eat something sweet, that food substance causes neuropod cells in the gut to send parallel signals to the brain which activates dopamine and tells us to seek out and eat more sweet foods
  • Dietary tribal ideology can hold you back from finding the right foods for your body
  • The distribution of fat in the body is more related to insulin signaling; the total amount of fat in the body is related to energy intake
  • The types of foods most addictive are generally a mix of carbohydrates and fat in optimal concentration which triggers dopamine and activates seeking behavior
  • When it comes to nutrition, author credentials are not indicative of the quality of information and publishers do not fact-check – be diligent and unbiased in your review or check out Red Pen Reviews (free to public)


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Stephan Guyenet is a neuroscientist focused on the neuroscience of obesity and energy homeostasis.  He is the author of the book, The Hungry Brain and founder/director of Red Pen Reviews. In this episode, Stephan explains how obesity has changed phenotypically over the course of human history as well as what might explain the dramatic increase in prevalence of obesity in the last few decades. He talks in depth about the role of genetics, the brain, and hormones like leptin play in the regulation of fat mass. He dives deep into two common theories of obesity—the carbohydrate-insulin model and the energy balance model and provides his take on which theory has stronger evidence. Additionally, he provides insights on how we’re hard-wired to think about food and the consequences of modern foods designed for maximal pleasure. Finally, he goes through the factors that affect body weight, set points, and provides takeaways for people wanting to take advantage of what we know about the brain’s role in regulating our body weight.

We discuss:

  • Stephan’s neuroscience background and his focus on the nuances of obesity [2:15];
  • How obesity has changed for humans throughout history [8:00];
  • The association between obesity and adverse health outcomes, the “obesity paradox,” and confounders when relating BMI to longevity [14:00];
  • The sharp increase in obesity across demographics [23:30];
  • The hypothalamus and its role in obesity [30:00]; 
  • The role of the hormone leptin in obesity [40:00];
  • The genetic component of obesity [46:30];
  • Understanding the tendency of humans to store fat through an evolutionary lens [57:00];  
  • The hedonic aspect of food, and how the brain reacts to modern, highly-rewarding foods [1:03:30];
  • How we are hard-wired to think about food [1:14:30];
  • A review of the “Carnivore diet” [1:21:45];
  • The energy balance model, carbohydrate-insulin model, and unifying the theories around adiposity [1:34:15];
  • Body weight set points: a hypothetical comparison of two individuals [1:41:45];
  • Takeaways for people who want to lose weight and keep it off [1:48:30];
  • Evidence that favors the energy balance model of weight gain [1:56:00];
  • The synergistic effect of fat and carbohydrates and observations that a low-fat diet or a low-carb diet can cause weight loss [2:04:30];
  • Red Pen Reviews [2:11:00];
  • More.

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