Discovery of Leptin: Hormonal Regulation of Appetite

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The discovery of leptin as a hormone that regulates appetite was a significant breakthrough in the understanding of obesity. Through experiments with obese mice strains, it was revealed that leptin is produced by fat cells and its levels in the blood directly correlate with body fat reserves. The leptin receptor, mainly expressed in the brain regions controlling hunger, receives signals from leptin. A decrease in leptin levels due to weight loss triggers a physiological response to starvation, leading to increased hunger, reduced energy expenditure, body temperature, and fertility. The presence of leptin forms a crucial feedback loop informing the brain about body fat reserves and the urgency to seek food.

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.