Hunger, weight loss and obesity | Stephan Guyenet, PhD

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In today’s world, many of us are struggling with being overworked, undernourished, and constantly stressed. Maintaining a healthy body weight is yet another challenge to stack on top of this, and for many, seems like an impossible task. As obesity rates rise and we are incessantly marketed a plethora of diets and weight loss solutions, it is difficult to navigate the path to better health.

In Episode #260, I’m joined by Dr Stephan Guyenet, a renowned researcher and authority on today’s subject. Together, we delve into the science behind eating behaviours, obesity, and the reasons why losing weight and keeping it off can be so challenging.

“There is no evolutionary incentive to evolve a really strong protective mechanism against fat gain. It looks like in most people there’s an asymmetry, where the system works really well at defending against fat loss, not as well against fat gain.”

Dr Stephan Guyenet is a highly respected researcher and expert in the field of hunger, weight loss, and obesity. With a BS in biochemistry from the University of Virginia, and a PhD in neuroscience from the University of Washington, he has dedicated over 12 years to studying neurodegenerative diseases and the neuroscience of body fatness. Dr Guyenet’s scientific publications have been cited more than 4,400 times by his peers, reflecting his contributions to the field. He is the author of the acclaimed book, The Hungry Brain, which was named one of the best books of the year by Publishers Weekly and deemed “essential” by The New York Times Book Review. Dr Guyenet is also the founder and director of Red Pen Reviews, a nonprofit that provides expert reviews of popular nutrition books, aiming to elevate the quality of nutrition information available to the public.

“Fat, carbohydrate, sugar and starch, salt, protein, and glutamate… the brain is wired to have a motivational response to these and that involves dopamine spiking in the brain. Dopamine generates that motivational response and reinforces behaviours related to acquiring foods that contain those nutrients.”

In this episode, we explore the widespread issue of obesity and how the brain plays a crucial role in our eating behaviours. Dr Guyenet explains the biological and psychological factors that contribute to weight gain, and the challenges that people face when trying to lose weight and keep it off. We delve into the different types of eating, including homeostatic and non-homeostatic eating, and how they influence our consumption of calories.

Dr Guyenet also sheds light on the importance of controlling our food environment and the reasons behind excess calorie consumption. We discuss various strategies for weight loss, from the impact of diet and exercise to Semaglutide and GLP-1 agonists. Throughout our conversation, Dr Guyenet shares practical advice and evidence-based insights to help listeners better understand the complexities of weight management and make informed choices about their health.

Specifically, we address:

  • Intro (00:00)
  • From neurodegenerative disease to obesity neuroscience (01:36)
  • The holiday weight gain (10:38)
  • The problem with excess fat (14:37)
  • ‘Personal fat threshold’ and diabetes (26:06)
  • Main drivers of type 2 diabetes (31:26)
  • The role of the hypothalamus in weight gain (38:55)
  • Homeostatic vs. non-homeostatic eating (47:29)
  • Genetics and the obesity epidemic (56:50)
  • Models of obesity: carbohydrate -insulin vs. energy balance (1:00:21)
  • The brain and obesity (1:10:34)
  • The protein-leverage hypothesis (1:19:39)
  • Carbohydrates, fat, and the Mediterranean diet (1:24:08)
  • The weight loss puzzle: low carb vs. low fat diet (1:30:10)
  • Foods that promote satiety on fewer calories (1:38:25)
  • GLP-1 agonists (1:43:08)
  • Is weight loss largely dependent on exercise? (1:55:06)
  • Physical activity vs sedentary lifestyle (1:58:40)
  • Mental health and sleep (2:00:28)
  • Expert advice on how to stop overeating (2:05:11)
  • Outro (2:05:59)

As obesity and weight management continue to be such prevalent issues, I hope this conversation with Dr Guyenet has provided valuable insights and practical strategies that you can apply to your own life or share with your loved ones. Thank you for joining me on The Proof’s journey towards better health and well-being for ourselves and our broader communities.

To connect with Dr Stephan Guyenet, you can find him on Twitter or visit his website, You can also purchase Dr Guyenet’s widely acclaimed book, The Hungry Brain, to learn more about why we overeat and how to overcome this issue. Make sure to also check out Red Pen Reviews, where you can access free expert reviews on nutrition books.

The best way to support the show is to use the products and services offered by our sponsors. To check them out, and enjoy great savings, visit

Enjoy, friends.


Supporting studies

  • A Satiety Index of Common Foods • PMID: 7498104
  • Obesity: the protein leverage hypothesis • PMID: 15836464
  • Normal weight individuals who develop type 2 diabetes: the personal fat threshold • PMID: 25515001
  • The carbohydrate-insulin model: a physiological perspective on the obesity pandemic • PMID: 34515299
  • Tirzepatide Once Weekly for the Treatment of Obesity • PMID: 35658024
  • Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity: a meta-analysis • PMID: 34981419

More about Stephan J. Guyenet, PhD

After completing a BS in biochemistry at the University of Virginia, Stephan completed a PhD in neuroscience at the University of Washington, then went on to study the neuroscience of obesity and eating behavior as a postdoctoral fellow.  He has spent a total of 12 years in the neuroscience research world studying neurodegenerative disease and the neuroscience of body fatness.  His publications in scientific journals have been cited more than 4,400 times by his peers. His book, The Hungry Brain, was named one of the best books of the year by Publishers Weekly and called “essential” by The New York Times Book Review.  He is the founder and director of Red Pen Reviews, a nonprofit that publishes free expert reviews of popular nutrition books.

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