Genetics Loads the Gun, Environment Pulls the Trigger

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Body weight is heavily influenced by both genetics and environmental factors, with heritability estimated at around 80%. While genetics determines an individual's predisposition to be lean or obese, environmental changes shift the overall population's body weight distribution, leading to increased obesity rates. Genetic variations dictate how sensitive individuals are to their surroundings, particularly concerning the availability of palatable, ultra-processed foods. Historical experiments demonstrate that dramatic calorie restriction can induce weight loss in anyone, illustrating that individual weight management is complex and reliant on the interaction between genetic predisposition and environmental influences.

In this episode, my guest is Dr. Zachary Knight, Ph.D., a professor of physiology at the University of California, San Francisco (UCSF), and Howard Hughes Medical Institute (HHMI) investigator. We discuss how the brain controls our sense of hunger, satiety, and thirst. He explains how dopamine levels impact our cravings and eating behavior (amount, food choices, etc) and how we develop and can change our food preferences and adjust how much we need to eat to feel satisfied.

We discuss factors that have led to the recent rise in obesity, such as interactions between our genes and the environment and the role of processed foods and food combinations. We also discuss the new class of medications developed for the treatment of obesity and diabetes, including the GLP-1 agonists semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro). We discuss how these medications work to promote weight loss, the source of their side effects, and the newer compounds soon to overcome some of those side effects, such as muscle loss.

Dr. Knight provides an exceptionally clear explanation for our sense of hunger, thirst, and food cravings that translates to practical knowledge to help listeners better understand their relationship to food, food choices, and meal size to improve their diet and overall health.

For show notes, including referenced articles and additional resources, please visit hubermanlab.com.