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

**Andrew Huberman** (0:00)
welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Zachary Knight. Dr. Zachary Knight is a professor of physiology at the University of California, San francisco, and an investigator with the Howard Hughes Medical Institute. For those of you that don't know, Howard Hughes Medical Investigators are selected from an extremely competitive pool of applicants and have to renew in order to maintain their investigatorship with the Howard Hughes Medical Institute every five years or so, placing him in the most elite of categories with respect to research scientists. His laboratory focuses on homeostasis, in particular, what drives our sense of hunger, what drives our sense of thirst and what controls thermoregulation, which is the ability to maintain body temperature within a specific safe range. Today, we mainly focus on hunger. Dr. Zachary Knight explains the biological mechanisms for craving food, for consuming food. And believe it or not, you have brain circuits that actually determine how much you're likely to eat even before you take your very first bite. And he explains the biological mechanisms for satiety, that is the sense that one has had enough of a particular food or food group. Dr. Knight also explains the role of dopamine in food craving and consumption, which I think everybody will find very surprising because it runs countercurrent to most people's understanding of what dopamine does in the context of eating and other cravings. Today's discussion also includes a deep dive into GLP-1, glucagon-like peptide and the novel class of drugs such as Ozempic and Mounjaro and other related compounds that are now widespread in use for the reduction in body weight. Dr. Knight explains how GLP-1 was first discovered and how these drugs were developed, how they work and importantly why they work and how that is leading to the next generation of so-called diet drugs or drugs to treat obesity, diabetes and related syndromes. We also discussed thirst and the intimate relationship between water consumption and food consumption. And we also talk about the relationship between sodium intake, water intake and food intake. By the end of today's conversation, you will have learned a tremendous amount about the modern understanding of hunger, thirst and salt intake, as well as this modern class of drugs, such as Ozempic and related compounds, all from a truly world-class investigator in the subjects of researching hunger, thirst and thermal regulation. Before you begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is BetterHelp. BetterHelp offers professional therapy with a licensed therapist carried out entirely online. I've been doing weekly therapy for well over 30 years. Initially, I didn't have a choice. It was a condition of being allowed to stay in high school, but quickly I realized that therapy is an extremely important component to our overall health. In fact, I consider doing regular therapy as important as getting regular cardiovascular exercise and resistance training, which of course I also do every week. Now there are essentially three things that great therapy provides. First of all, it requires that you have a really good rapport with the therapist, somebody that you can trust and talk to about what's really going on in your life. 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