How to Control Hunger, Eating & Satiety | Huberman Lab Essentials
Date: 2025-02-27 | Duration: 00:34:53
Transcript
0:00 Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I’m Andrew Huberman, and I’m a professor of neurobiology and ophthalmology at Stanford School of Medicine. 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. Today, we’re going to talk about
0:30 how hormones impact feeding and hunger, as well as satiety—the feeling that you don’t want to eat or that you’ve eaten enough. Now, it’s important to understand that hormones don’t work alone in this context. Today, I’m going to describe some hormones that have powerful effects on whether or not you want to eat more or less, or stop eating altogether, but they don’t do that on their own. They do that in cooperation with the nervous system. The first thing that you need to know about the nervous system side—the neural control over eating and hunger—is
1:00 that there’s an area of your brain called the hypothalamus. Now, the hypothalamus contains lots of different kinds of neurons doing lots of different kinds of things. There’s a particular area of the hypothalamus called the ventromedial hypothalamus, and it’s one that researchers have been interested in for a long time in terms of its relationship to hunger and feeding. The reason is it creates these paradoxical effects. What do I mean by that? What they found was that sometimes lesioning or disrupting the neurons in
1:30 the ventromedial hypothalamus would make animals or people hyperphagic—they would want to eat like crazy—and other lesions in other individuals or animals would make them anorexic; it would make them not want to eat at all. It would make food aversive. That means that the ventromedial hypothalamus is definitely an interesting control station for hunger, feeding, and satiety, but it doesn’t really tell you what’s going on at a deeper level. In fact, it’s a little bit confusing or paradoxical. It turns out that there are multiple populations of
2:00 neurons in there: some are promoting feeding and some are promoting not feeding or not eating. Now, the other neural component of all this that you need to know about actually has to do with your mouth. There’s an area of your cortex—that’s a little bit further up in your brain—called the insular cortex, and it processes a lot of different kinds of information, mostly information about what’s going on inside you, so-called interoception. The insular cortex has neurons that get input from your mouth, from the touch receptors in your mouth.
2:30 The insular cortex has powerful control over whether or not you are enjoying what you’re eating, whether or not you want to avoid what you’re eating, whether or not you’ve had enough, or whether or not you want to continue eating more. That has to do with the touch or sensation of eating. But the key point right now is to know you’ve got these two brain areas: the ventromedial hypothalamus that’s involved in hunger and lack of hunger, and you have this insular cortex that gets input from your mouth and cares about chewing and the
3:00 consistency of foods and all sorts of interesting things that are tactile. I think most people think about the taste receptors on the tongue, but we often don’t think about the touch or tactile essence of food. Now, let’s get back to the ventromedial hypothalamus. Sometimes it makes animals or people want to eat more, sometimes less. So what’s going on there? There’s a classic experiment that was done in which researchers took two rats and parabiosed them to each other. What that meant is that they did a surgery
3:30 and they linked their blood supply so that they were forever physically linked to one another and could exchange factors in the blood. But their brains were separate, their mouths were separate, and they essentially did everything separately, except that they were linked to one another. They had to walk together and go to the same places in order to do it. This parabiosis experiment revealed something really important. When they lesioned the ventromedial hypothalamus in one of the rats that was connected to the other rat, that rat got very fat—just really obese. The other one,
4:00 however, got very thin; it actually lost weight. So what does this tell us? This tells us that there’s something in the blood that’s being exchanged between the two animals because it was their blood supply that was linked. That tells us that there are hormonal or endocrine signals that are involved in the desire to eat, hunger, and appetite. Next, we’re going to talk about what those endocrine signals are, and then I’m going to immediately point to some entry points that you can use. You can use
4:30 these even if you’re not parabiosed to anything, and that can allow you to time your meal frequency and predict when you’re going to be hungry or not. Let’s talk about the endocrine factors that regulate feeding, hunger, and satiety. One of the really exciting things to emerge in this science of feeding and appetite in the last 20 years is the discovery of another brain area, not just the ventromedial hypothalamus, but an area of the brain called the arcuate nucleus. The arcuate nucleus has some
5:00 really fascinating sets of neurons that release even more incredible molecules and chemicals into the blood, and these chemicals act as accelerators on feeding and appetite, or brakes. First of all, there are a set of neurons in this arcuate nucleus: the pro-opiomelanocortin system. Now, the POMC neurons make something called alpha-MSH, alpha-melanocyte-stimulating hormone. Alpha-
5:30 melanocyte-stimulating hormone (MSH) reduces appetite, and it’s a powerful molecule. So just put that on the shelf: MSH reduces appetite. Now, there’s another population of neurons in the arcuate nucleus called the AgRP neurons. The AgRP neurons stimulate eating. The activity in these AgRP neurons goes way up when animals or people haven’t eaten for a while, and the activity of MSH—the
6:00 release of MSH—goes up when we’ve eaten. Next, let’s talk about a hormone peptide that activates hunger, and this is a really interesting one because it relates to when you get hungry in addition to the fact that you get hungry at all. It’s called ghrelin. Ghrelin is released from the GI tract, and its main role is to increase your desire to eat. It
6:30 does that through a variety of mechanisms. Part of that is to stimulate some of the brain areas—the actual neurons—that make you want to eat. In addition, it creates food anticipatory signals within your nervous system, so you start thinking about the things that you happen to like to eat at that particular time of day. This is fascinating. Ghrelin is like a hormonal clock that makes you want to eat at particular times. Now, the signal for ghrelin is
7:00 reduced glucose levels in the blood. If it drops too low, ghrelin is secreted from your gut and it activates neurons in your brain at various locations. We all know about the famous Pavlovian experiments of Pavlov’s dogs—they start salivating to the bell after the bell was presented with food. You remove the food, and then just the bell can stimulate the salivation. We become Pavlovian at times, but rarely is it ever discussed what the neural pathways for that are. It turns out that these hormones that are secreted from the gut can stimulate the neurons to create a
7:30 sensation and a desire for certain foods at certain times of day. You’ve done this experiment if you are somebody who eats breakfast at more or less the same time each day—let’s say 8:00 a.m. Your ghrelin secretion will start to match when you typically eat, and it’s able to override the low levels of glucose in your bloodstream because the ghrelin system also gets input from a clock in your liver that is linked to the
8:00 clock in your hypothalamus in your brain. What this means is if you eat at regular meal times, you’ll start to get hungry a few minutes before those meal times. If you’ve ever wondered why your stomach starts to growl because it’s a particular time of day, and you’re like, “Oh, I must want to eat,” well, that’s ghrelin. Ghrelin is secreted as a kind of food anticipatory signal to get you motivated to go eat at regular times. But what that means is that if you suddenly go from
8:30 eating on a very regular schedule to skipping a meal, or pushing your meal timing out, or shifting it at all, you’re going to have ghrelin in your system. That ghrelin is going to stimulate the desire to eat by acting at the level of your brain. Ghrelin stimulates the AgRP neurons, which makes you want to eat. Regularity of eating equals regularity of ghrelin secretion, which equals regularity of activity of these AgRP neurons, meaning you will be hungry at very regular intervals. So if MSH inhibits feeding and makes us want to eat less, and ghrelin
9:00 makes us want to eat more, there’s another hormone called CCK, cholecystokinin, that is potent in reducing our levels of hunger. CCK is in the GI tract; it’s released from the GI tract, and its release is governed by two things. One is a subset of very specialized neurons that detect what’s in the gut—the specific contents of the gut—and by certain elements of
9:30 the mucosa, the mucous lining of the gut, and the gut microbiome. What’s really interesting is that CCK is stimulated by fatty acids, amino acids, and particular amino acids that we’ll talk about, as well as by sugar. Which fatty acids in the gut stimulate the release of CCK? Omega-3 fatty acids and conjugated linoleic acid (CLA), either
10:00 from food or from supplements, stimulate the release of CCK, which then reduces or at least blunts appetite. The other thing that stimulates CCK that I mentioned are amino acids. When we eat, we have the ability to break down different macronutrients—carbohydrates, fats, or proteins—into sugars and glucose that we can then convert to ATP. Remember the Krebs cycle from high school? We’re not going to go into that today; that’s for a future episode. Amino acids
10:30 can be used as energy through a process called gluconeogenesis, converting proteins into energy, or those amino acids can be broken down and then rebuilt into things like repairing muscle tissue as well as other forms of cellular repair. They’re involved in all sorts of things related to protein synthesis. What does this mean? If we eat the proper amino acids at the proper levels, if we ingest omega-3s and CLAs at the proper levels or get them from supplements,
11:00 there is a blunting of appetite. Appetite is kept clamped, and we don’t become hyperphagic; we don’t overeat. We tend to eat within healthy or normal ranges. This is very important because most people don’t understand that when we’re eating, we are basically fat foraging and amino acid foraging. In other words, even if it’s not conscious, we are eating until we trigger the activation of CCK. Now, there are other reasons why we shut
11:30 down eating, too. The volume of food in our gut can be large and we can