How Hormones Control Hunger, Eating & Satiety

Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine, opens this installment of a month devoted to hormones. The previous episode covered estrogen and testosterone; this one covers how hormones shape hunger, feeding and satiety, which he defines as the feeling that you don't want to eat or that you've eaten enough. Before the science he reads sponsor segments for InsideTracker, Athletic Greens and Munk Pack. In the Munk Pack segment he describes his own routine: he says he follows neither a keto nor a high-carbohydrate diet, keeps carbohydrates low during the day to support alertness and focus, and eats carbohydrates at night to ease the transition to sleep.

His central framing is that hormones do not act on appetite alone; they act "in cooperation with the nervous system." He promises a lot of biology along with several "entry points" for tools that affect hunger, meal timing and satiety. Most of these are behavioral, but he says he will also cover supplements and some brain-machine interface devices.

they don't do that on their own, they do that in cooperation with the nervous system.

The first neural structure he introduces is the hypothalamus, at the base of the forebrain. He describes it as a set of control centers containing neurons for sexual behavior, body temperature, circadian rhythms, sleep and wakefulness, and even rage. Within it, the ventromedial hypothalamus (VMH) has long interested feeding researchers because its effects look contradictory.

Huberman reports that lesioning or disrupting VMH neurons sometimes made animals or people hyperphagic, so that they "would want to eat crazy," while other lesions made them anorexic and made food aversive. He takes this to mean the VMH is clearly a control station for hunger and satiety, but the lesion results alone do not show what is going on at a deeper level. He says the explanation is that the region holds several populations of neurons, some promoting feeding and some suppressing it. In his words, the VMH is "sort of an accelerator and a brake on feeding."

The second neural component involves the mouth. Huberman describes the insular cortex as processing interoception, information about what is going on inside the body. It receives input from the mouth's touch receptors. He says it has powerful control over whether you enjoy a food, want to avoid it, feel you have had enough, or want to keep eating, and that this depends partly on the touch or sensation of eating rather than only on taste.

He uses himself as an example. He says he enjoys "the mere act of chewing" and likes chewing celery sticks for the sensation itself. From this he draws a practical point: chewing celery, cucumber slices or gum that has no sugar or caloric content generally will not drive increased hunger. Sugar is different. He says it acts in a specific way in the insular cortex and other parts of the nervous system to promote the desire to eat more, a mechanism he says he will explain later.

He also argues that texture preferences are individual and probably learned. His example is sea urchin at sushi restaurants: he dislikes its consistency, while others love it. He suggests cultural background, such as being raised eating urchin, may play a part, and concludes that "touch has a lot to do with whether or not you want to eat or not."

To resolve the VMH puzzle, Huberman describes a classic experiment in which two rats were parabiosed: surgically joined so that their blood supplies were linked, while their brains and mouths stayed separate. When researchers lesioned the VMH in one rat, that rat became very obese. Its partner became thin and lost weight even though it ate the same amount of food it had eaten before the lesion.

His inference is that, because only the blood supply was shared, some factor in the blood passing between the animals must have changed the partner's weight. This points to hormonal, or endocrine, signals involved in hunger and appetite. He presents this as the bridge to the rest of the episode, which covers what those signals are and how they can be used to time meals, predict hunger, and either reduce or increase appetite.

He explains why the topic matters. Some people are trying to eat more, but he thinks far more are trying to eat less, and he says the data point to "essentially an epidemic of diabetes, type II diabetes and obesity." He adds that most people now agree that maintaining a healthy body weight and body composition is one of the best paths to longevity and wellbeing, and that cognitive functioning is linked to levels of adipose tissue.

Huberman calls the arcuate nucleus one of the most exciting findings in feeding research of the last 20 years. He says its neurons release molecules that act as accelerators or brakes on feeding and appetite, and that these molecules can be influenced through simple behaviors.

The two neuron populations he describes: - POMC (proopiomelanocortin) neurons, which make alpha-melanocyte-stimulating hormone (alpha-MSH). He says MSH reduces appetite and that MSH release rises after eating. The "melano" prefix reflects a link to melanin and pigmentation, which connects to the previous episode's discussion of light, dopamine and melanin. - AgRP neurons, which stimulate eating. He says their activity rises sharply when animals or people have not eaten for a while (not necessarily long-term starvation). He links them to the autonomic ramp-up some people feel when approaching food, such as excitement, anxiety or even a slight resting tremor, in people without any eating disorder.

MSH reduces appetite and it's a powerful molecule, all right?

His evidence for AgRP's role comes from loss and gain of function. He says killing AgRP neurons makes animals and people stop eating and become anorexic, a term he notes is used in the scientific literature for a behavior pattern as well as clinically. Stimulating them makes animals or people eat to the point where they burst. He says AgRP connects to the earlier VMH discussion but defers that link to later in the episode.

Huberman says MSH is released from the medial pituitary, a gland close to the hypothalamus, and that it promotes the desire to stop eating. His key claim is that MSH release is activated by ultraviolet light to the eyes, not to the skin or the pituitary directly. He says "this has been shown over and over again," and presents it as another reason to get ample light, ideally sunlight, throughout the day.

He uses this to explain seasonal patterns. In his account, animals and people eat less in spring and summer, and humans generally have greater appetite in cold winter months. He says that is not only because of holidays and abundant food: with ample sunlight to the eyes, the signal reaches the MSH-releasing POMC neurons and keeps "the break on appetite in check." He treats hibernating animals as a separate case because they eat little while in burrows or dens. He also notes that bears do not technically hibernate by scientific criteria but enter a kind of torpor.