Dr. Zachary Knight: The Science of Hunger & Medications to Combat Obesity

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.

Articles

• Chronically Decerebrate Rats Demonstrate Satiation But Not Bait Shyness (Science)
• Recombinant Leptin for Weight Loss in Obese and Lean Adults: A Randomized, Controlled, Dose-Escalation Trial (JAMA)
• Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits (Cell)
• The Biology of Human Starvation: Volume I (University of Minnesota Press)
• Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake (Cell Metabolism)
• Changes in Energy Expenditure Resulting from Altered Body Weight (The New England Journal of Medicine)
• Energy Balance After Sodium–Glucose Cotransporter 2 Inhibition (Diabetes Care)
• The Origin and Understanding of the Incretin Concept (Frontiers in Endocrinology)
• The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent (Toxicon)
• Once-Weekly Semaglutide in Adults with Overweight or Obesity (The New England Journal of Medicine)
• Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (The New England Journal of Medicine)
• LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept (Cell Metabolism)
• Cholecystokinin decreases food intake in rats (Journal of Comparative and Physiological Psychology)
• Dopamine subsystems that track internal states (Nature)
• Water and sodium intake of wild and New Zealand rabbits following angiotensin (Peptides)
• Thirst—and Brain Control of Water Balance: Recent research on thirst suggests that sodium-sensitive receptors near the third ventricle participate in the control of the complex balance of fluids in the body (American Scientist)
• A gut-to-brain signal of fluid osmolarity controls thirst satiation (Nature)
• Thirst neurons anticipate the homeostatic consequences of eating and drinking (Nature)
• The Forebrain Thirst Circuit Drives Drinking through Negative Reinforcement (Neuron)
• Mind over milkshakes: Mindsets, not just nutrients, determine ghrelin response (Health Psychology)

Huberman Lab Episodes Mentioned

• Healthy Eating & Eating Disorders - Anorexia, Bulimia, Binging
• Dr. Anna Lembke: Understanding & Treating Addiction

People Mentioned

• Jeffery Friedman: professor of genetics, Rockefeller University
• Douglas Coleman: professor emeritus, Jackson Laboratory
• Kevin Hall: integrative physiology, National Institute of Health
• Richard Palmiter: professor of biochemistry, University of Washington