Neuroscience of overeating

From micro TV, this is Twin, this week in neuroscience episode number 66 recorded on November 17th, 2025. I'm Vincent Rackiniello and you're listening to the podcast all about the nervous system. Hey, joining me today from New York, Tim Chung. Hello, hi, everyone. Good to be back in this bitzily cold and not bitzily cold. A fairly cold day. Winter's coming, which is a little scary. It is. Finally, it's on its way. Also joining us from New Orleans, Vivian Morrison. Hello. Where it's probably never going to be winter, right? I mean, last year, it snowed. It's snowing. Oh, yeah, it was snowing. Don't know this. I forgot. No, it's like a disaster trap. I don't know, like, there's poor folks. No, but last year, we had a big, in January, we had a, well, so it's not last year, but past winter, we had a big snow storm. Like, it was like a snow. And do like in England, whenever it's snow, snow, so rarely in England that, whenever it snows, the whole country shuts down, like even if it's like an inch or snow, is that also the same in New Orleans? Yeah. Yeah. Yeah, I mean, but it's, you know, it's basically like a flood, right? It's just frozen water and we flood all the time, so yeah. But today is something but now, now I've forgotten it. I didn't have to do it. Oh, you have to go like this. Apparently, you have to go like this. Shake your head. Shake your head left to right. I don't know. My husband was like, shake your head, left to right. You'll remember. And I was like, oh my gosh, I remembered if it doesn't work, he must be broken. Now, what I find is I have to think about it for a while, but that would mean I have to be silent and in a podcast is not really conducive. But does it? So this is actually quite interesting, in terms of neuroscience. So as you get older, the harder it is to retrieve memory, everyone comes across this as an SI kind of rapidly age. I also find the same. And I don't think anyone knows. I have tried to look up studies that kind of study into this like, why as you get older, it's harder to retrieve. And for me, there's nothing I can do about it. It would usually something that I do someone's name or some sort of weird facts, it would just randomly pop into my head like a day after and without any prompting. Yes, it did happen. In fact, I just remembered what I wanted to say, but excellent. But you know, I have problems with people's names, but I can remember names from years ago. No problem. Right. So that's another finding. Sorry to say, we all go through this. The same as people with dementia is that childhood memories and earlier memories are much more easily retrievable than the, as you get older, the memory is fade. And it's maybe, I mean, there are hypothesis about why that is like the childhood memory. You have more rehearsals in your head, like you can get to practice more. But they're not as actually real. Like because each time you go through it, it's like your memory is of the replay. So it ends up not necessarily lining up with reality, but at least it's there. At least the fake version, you can reach, you know, it doesn't make version. I suppose you're just completely blanking as you see someone. I don't have any childhood memories. So, you know, like, I'm screwed. I'll have nothing to remember. I find if I focus, if I focus, eventually I can remember. So here's what I wanted to tell you. I was on the plane back from LA yesterday. I went to a David Baltimore Memorial. And, you know, there's a screen in front and there's a everybody's screen. It's got Spotify. And it's got like six podcasts as just selections you could listen to. And one of them is the the Huberman podcast, right? A neuroscience podcast. I'm like every person on this plane is going to see his face. You know, he's got millions of listeners. We need to get twin on the back of the airline seats. Yeah. That's because he does self-help stuff. So you had to have memory and had to live longer and had to see farther and all that stuff. And people eat that. And this is what we do. We tell you there's nothing you can do. It's just genetics. I'm today we're going to have a little information for you, which may be a Huberman relatable thing, I think. I have an eye out. Don't even draw. I'm sorry. Well, we're different because we do papers and, you know, we don't do woo-woo science. But there's certain topics that people relate to. And dementia is one of them. We've talked about that a lot. And memory is another one. And today it's all about overeating. This is a cell, a neuron paper. It's actually a review. And it's open access. So everyone can read it. It's called the neurobiology of overeating. So I saw this title. I scrolling through my RSS fees. I said, oh, that's it. And then I started to read it. And I said, I am way over my head because I'm a virologist. I really don't know much about the nervous system. But I thought, you know, I have two neurobiologists with me. And I thought it would be interesting. So this is by Garrett Stuber, Valerie Schwitz Gable, and Christian Luscher, who are, let's see, at the University of Washington, which is Seattle. There's Swiss people. And then Swiss. We have Geneva University, hospitals, and University of Geneva. Were you there? No, I was at Lausanne. But, you know, if this is like Geneva on the west side near France, you have Geneva. And then halfway, I was halfway across the lake essentially. But yeah, yeah, I took a train to Montreux last two years ago. And you go for Geneva, you pass through Los Angeles. Really, they lived in Montreux. Yeah, they lived there. They lived there for the past 20 years. Yeah. Oh, it is. It is. You should live there, man. It's beautiful. Dude, I'm trying. I'm trying. You're trying to live there? Okay. Yeah, trying to find a way to get back there. The train, and then you go back to Geneva, you get on it. Montreux, you go through Los Angeles, and then, and on the way, you know, it's very cool. The slopes have these little private vineyards on them, right? But they make little local wines that nobody will ever get outside of Swiss wine. Yeah. Oh, okay. Intriguing. I've been thinking I've ever had Swiss wine before. Vivian looked absolutely insulted. Anyway, this is all about, you know, I'm not, I'm not insulted because, oh, you're allowed to export Swiss wine. Nobody is it like a local. I don't know. I don't think they, I don't think they explored it. Yeah. Okay. That's why I'm sorry. At least the little family vineyards. Yeah. Sorry. What about Vivian? Well, why was just going to say this is somewhat related, you know, it's the the confluence of Switzerland and the paper today is that Swiss gruyère, the cheese, was voted the best cheese in the world on the 13th of November 2025 at the World Cheese Awards. So what, sorry, what cheese again? Can you say that word? Gruyère. Gruyère. Oh, exactly. I was like, you mean gruyère. Gruyère. Yes. The proper pronunciation is whatever you just said. Oh, you know, it's, you know, it's interesting. Speaking of cheese, guys, I was in Netherlands, right? And there's a town which the cheese is named after. It's spelled G-O-U-D-A in my whole life. I called it huda, right? But the train guy says, next stop, how da? How da? Yeah, but we don't want to be those people. And I should, I'm just, this is, I shouldn't have done that. It's like, you don't want to be like, I'm going to parry. I'm going to huda. It's how Vincent, Vincent van Gogh, or however you pronounce it, like if you say that in Netherlands, they would just spit in your face. How do you say Vincent van Gogh, Vincent van Gogh? Something like, I'm not Swiss. No, I'm not Dutch. Anyway, we're talking about food, because that's the topic of this paper. It's about obesity and the prevalence, they, they, as I said, this is a review article where they're going to quote results from many different papers. And I will try to synthesize it for you. The prevalence of obesity is increasing and they say it's predicted that in 2035, more than half the adult population of 40% of children will be overweight. So overweight is defined as a body mass index or BMI, over 25 kilograms per square meter. And obesity is BMI over 30 kilograms per square meter. And this is not just the U.S. and not just, what did it quote? It's high income country. High income countries, they say developing, but you're not supposed to use that anymore. High income, middle income, low income, it, it affects all income countries. Actually, in fact, as the low income or like developing countries become more economically kind of higher up, I think the danger is that they go from underweight straight away to obese. That's something that people are married by. And it's also the diet, the Western diet. Yeah, exactly. And largely driven by kind of rich food that Vincent would tell us about. Well, so in fact, this being overweight is a problem because you have other health issues as a consequence, right? That's the real issue you can have, well, increased death disease, diabetes, cardiovascular diseases, cancers. And so, I mean, this is called an obesity epidemic. And as you'll see in the paper, some people call it food addiction, but it's not clear that it's actually addiction as in a drug addiction or not. We'll talk a little bit about that. So how do you get obese? Well, overeating is like the main thing. And they say, which is very interesting, you could be obese and exercise your heads off. And it probably wouldn't help all that much. Enhancing physical activity may be insufficient to prevent overweight, or we store normal weight in individuals with obesity. That's very interesting. So why are people gaining weight, calorie dense foods? And in particular, I didn't know this, foods that combine high levels of fat and sugar together. That promotes overeating. And that's a combination that you don't find in natural foods, except cashews, coconut, and durian. You had to look up durian. It's my favorite food. It smells terrible. It's one of my favorite foods since I'm from that area. So it smells like cat poo. It's hot trash. No, well, cat poo on fire, maybe. It smells kind of pungent. I don't actually know what they've probably done like MS to figure out what is the aromatics. That makes us smell really bad. But you know it's good because in Southeast Asia, where durian is grown, all the monkeys go crazy for durian. The smell is really, it travels a long way. So in Singapore, you can't even bring durian in public transport. I think it's against the law, because it smells so bad. But then monkeys would travel four miles to go to durian tree when it's ripe and get it, because it is the tastest, it's hot too. It's kind of like a little bit sweet fermented cheese, perhaps, is how I describe it. So anyway, cashews, I like cashews, but maybe I should stay away from them now. So in general, you know, it's like the serving size is like this. It's like 12 almonds. Yeah, on an airplane, they give you a little cup of like 12 nuts. Anyway, but there are other foods that have this high common, not natural foods, but the processed products, right? We're all here about trying not to eat too much processed food. Like milk chocolate is a highly processed food and ice cream. I hear cereals. Anything you buy in a box is highly processed too. Milk, but milk, it has fat and sugar, but they say it's rarely consumed in excess. And yeah, I know, because I don't like the taste of milk. I just use it on cereal. I would never just drink a glass of milk. Would you guys drink a glass of milk? I mean, after like eating, after eating another, we call them, in my family, call them UHPs, ultra, or no, UPFs, UPFs, that's what it is. Ultra processed foods. So after eating like an Oreo or a cookie, you could eat milk. Yeah. Yeah. But just like a glass of milk, like just out of nowhere. So they cite a study where it shows that if you offer people an ultra processed diet exclusively ultra processed, they will increase their intake, their daily coloric intake by 500 K cows, 500,000, right? 500 K cows a day. And they think that this is the origin of food addiction, which they have in quotes. So there's a paper they cite here, which is a hypothesis about food addiction, that if you get continually exposed to palatable food with high coloric density, which is what we're talking about, this is overrides your metabolic needs and you lose control over your food intake. And just a quick point, Vincent mentioned earlier, naturally, we don't really see much of this combination of high carbohydrate and high fat. So especially sweet and fat. So we probably didn't develop kind of any evolutionary way of stopping eating too much. So when we manufacture food, that has that combination, it's kind of can be deadly. Yeah. Anyway, so this is what they're going to talk about here, the neurobiology, the anatomy and physiology of neuro systems that control feeding behavior. And I learned like tons, which is what I wanted to do here. So this is an open access paper. And there's a nice figure figure, one that maps all on the brain, all of the places with that control, all the circuits and regions that control eating behavior. And the so the first we have to talk about homeostatic and hedonic feeding systems. So I understand homeostasis, right? But hedonic, I didn't know, but hedonic is the part where you just eat because it tastes good. Yeah. And homeostatic you eat because you need nutrition. Right. Right. So they say it's very fun. It's common sense that when you're hungry, it drives eating. And that relieves the negative state associated with hunger. And that then that's it. And you stop eating. In most cases, people stop eating when they're satid. Okay, that's a word we'll use when you're satid. When you've eaten enough, you stop eating. But they know, go ahead, go ahead. Yeah, you feel full. You feel full. Yeah. But they say highly palatable food can override satiety, which is the adjective, I guess. Yeah, the feeling of fullness, feeling of fullness. And then you will eat even when you're not hungry. And so that's what dessert is at the end of a meal, no, at the beginning. Because you wouldn't want it unless it were really sweet, right? Yeah. It's because what they like, the hypothesis is that once you're full, you only seek out the high fat, high sugar food. So that's what dessert is. And that's why it comes at the end. Because at the end, like you probably won't want to eat us after you've got yourself on a steak and like a cream spinach, whatever. Someone give you like a salad or or maybe even, I don't know, cheese, a cheese board. But someone give you a salad, you probably won't touch it anymore, but like someone give you a nice, nice dessert. You were so easy. It's interesting that the order of salads and main dishes is different in different countries, you know? In some places they put the salad first, kind of wet your appetite, right? And then you dig into something else. I can eat a salad after a main dish. I typically don't, I'm full by the time dessert comes. Unless it's crème brûlée and then I will have it because I love crème brûlée. Best dessert ever. Not just sugar and fat, but also caramelization too. But also most places don't have it, so it's good. Do you have crème brûlée? No. Okay. That's it. I'm done. Give me the bill. But anyway, this, they say overeating, it may be evolutionary advantage in animals because they can store fat, right? We're tougher times, so maybe that's one of the origin. Which I think they see also in like, intimate populations, places where the availability of food really fluctuates. There's a period where it's like when the hunting is good, they eat and they eat and they eat and they eat and they, as much as they can, and then they gain a bunch of weight because they know there's going to be a time when the, you know, game is not available. Right. It would not do well. It's just like it, but like hibernating bears and you see quite a lot of other organisms that do this. Yeah. I think we don't have that same time. Because we invented farming. Yeah. Yeah. I'm reading a book called Pathogenesis and it talks about how the, there's some thought that the arrival of agriculture was like one of the main drivers of everything that goes wrong. Everything that goes wrong. Yeah. It's like, you know, you bring people, people come together. Yeah. From disease to fake news. It's all because of farming. This is, so this is, hunger driven eating and pleasure driven, umiostatic and hedonic. And obviously there's going to be an interplay, right? They're not just one or the other. They play into each other as we're going to talk about in this paper. So that's what regulates our feeding this homiostatic system and the hedonic system and the homiostatic, of course, the goal is to maintain a certain weight and to keep your energy stores there, right? And eating for enjoyment pleases you. It serves your mental well-being, but it can screw up your energy balance, right? But I think the, just to reiterate the point, I think that hedonic, the why you eat for pleasure is people, I think biologists has a hypothesis that it is to store up energy for leaner time potentially. It's evolved for your way to trick yourself to eat more because of leaner time might be coming. Yeah. So it turns out that the hypothalamus is a critical place for controlling food intake. And in fact, part of it does the hedonic and part of it does the homiostatic feeding. And you can see that in the picture there. And of course, that's connected to many other places in the brains in the brain that regulate feeding behavior as well. Okay. So within the medial hypothalamus, there are many nuclei that are connected. And two of these nuclei, collections of neurons, right, have been implicated in homiostatic feeding. The arqueut nucleus, which is arc, which Jason would not like because it's another arc. I think it was there before Jason's arc, most likely. And then the pair of ventricular nucleus, or the pvh. So yeah, there's a lot of abbreviations here. Hopefully we can remember them. Now in the arqueut nucleus, so these are two places that are involved in homiostatic feeding. In the arqueut nucleus, there are two gamma amino butyric acid, GABA response of neurons that mediate this, right? There are a goody related peptides or AGRP neurons. And these activate when you're hungry to promote feeding. And then there they proopio melanocortin or POMC, POMC neurons, which inhibit feeding when your energy stores or fine, right? Well done for pronunciation, that's pronounciating that. That's no way I could have done it. I know these words. And the thing is they've done single cell RNA transcriptomics and these areas are very diverse. It's not just one cell type. There are lots of different cell types that are doing different things that they call to me. The traditional view of POMC neurons as a homogeneous population must give way to a nuanced system where there are lots of other cells there. And they're references for that, but it's good enough just to know that these are heterogeneous areas. Okay, so the AGRP neurons are modulated by things like low blood glucose and a hormone called ghrelin. And the ghrelin is secreted by your stomach when you're fasting, when you're not eating. And this, I spoke to a person who worked on ghrelin and said, they had no idea it would be the stomach. They found ghrelin circulating. They said no idea that the stomach would be secreting it. Okay, so ghrelin is secreted by the stomach. And that's kind of interesting because how often is my stomach actually, my stomach, I think, is most of the time empty, even though I can feel full. Yeah, that's something interesting going on there. What do you mean, B, you can feel full, but your stomach is empty. But I don't know how long it will take after I eat a meal, how long it takes for my stomach to be gone, everything to pass down. Well, it varies depending on whether it was like a largely liquid or solid meal. That influences the sphincter opening between the stomach and the small intestine. But actually, I think it makes sense to have ghrelin be expressed by like the first stop. Because the other signals that are involved in like curbing intake, that's going to take those take time to ramp up and be secreted because this whole, I think it's maybe we'll come back to this, but you saying like I feel full, like what the heck does that mean? Like it's not that your stomach feels distended or at least not always, you know? So, you know, we'll probably touch on this, but like the your body needs to sense that there are fats and that you have reached a certain level of intake. That absorption doesn't happen until it's in, you know, in your small intestine and, you know, it needs time to, everything needs time to be broken down. And so like the signals can take like a fairly long time. So better to kind of like, I don't know what the word is like, better to have this signal that can kind of decrease as the stomach fills to allow the rest of the systems that are involved in leading to satiety to be increased till they start rising. Okay. So the Grelin is makes you eat and then there's another molecule called leptin, which makes you stop eating. So these neurons in the AGRP that we've been talking about are stimulated by Grelin and inhibited by leptin. And some say a population of leptin receptor, so there's a receptor for leptin. And a population of neurons that have leptin receptors, they also have GABA, they're GABA neurons. They make connections to these AGRP neurons. Now the POMC neurons are activated by satiety signals, right, which includes leptin and also insulin. It's another one. These are released by adipose tissue and the pancreas. So leptin comes out of adipose tissue insulin from the pancreas and that reduces your food intake. I don't know if they I really doubt that they talked about this because I'll be honest and say I didn't go through it with a fine tooth comb, but adipose tissue, you have like a lot of different deposits and sources of it in your body. And I think it is not yet like fully appreciated that those deposits of fat are like chemically and functionally different. So like the fat around and it's also based on sex. So like the fat around the hips of a woman are biochemically and functionally different than the fat that's around the breasts. So I would be interested to see if there are certain fat deposits that are bigger secretors of insulin or more sensitive to it because when somebody has liposuction, you're essentially removing like an organ if you want to consider adipose tissue like an organ. And just think about how that can mess your whole system up and I actually wonder to what extent it would make you eat more. Over eat. Yeah, that's a good question. You're getting liposuction to lose weight, but maybe the effect is make you eat more. Very interesting. Yeah. Well, if you have liposuction, you have to be careful because you could gain all that back again. I think and they have stem cells too. So I thought the idea is that if you do liposuction by sucking out all the fat cells, you are less likely to gain the fat back because the cells are actually gone. But they are stem cells. They're stem cells. So it's like with cancer, right? Did you get a total like totally like clean margin? I don't know how plastic is adipocytes, you know, transcriptional profile. Can it like D differentiate? I actually think that I do think that that cell type is particularly plastic. Like I think, you know, I do think there can be like D differentiation programs that would take like a mature adipocytes and turn it into a stem cell. But I'd have to, I'd have to, don't quote me on that. So these signals grow and leptin, and so they bind to receptors on these AGRP or POMC neurons, right? And then they say these project to many different brain regions. And that is how the balance between eating and not eating is is is made. And they go into this quite a bit, yes. Vincent, before we move on from the leptin and POMC neurons, can I quickly touch upon some cool facts about those guys? So listeners, if you guys are interested, if anyone listening is interested, look up, pause the podcast and then go to Google and look up OB-OB mouse. So this is a mouse that people have found to be deficient in leptin. And when you don't have leptin, you're, you just overeat massively because leptin is the molecule that tells you, you are, you are not starving. So when you don't have leptin, you think you're starving all the time and you eat crazily. And the OB-OB mouse is kind of like a Jabba the Hut off the mouse. It's completely ginormous. And related to this, I was listening, I was watching a, like a role institution lecture by a guy called Dr. Charles Yao, I think that's his name, he's from a University of Cambridge. And he was telling, he was lecturing on obesity and he was talking about how, apparently, I didn't know this, for people who have dogs, apparently the best dog to be, to use for guide dogs are Labrador Retriever. So they are very, very nice dogs, they are very docile and they are super food motivated. And that's why they're very trainable. And if you look around, like if you go out on the street and you see a guide dog, often they are Labrador and they're a little bit chunky, full of chunk as the kids call them. And the reason why they, this team from University of Cambridge found out the reason why is because these Labrador Retrievers have a mutation in the POMC gene to make it deficient. So that means that these, and this is enriched in the Labrador population, relative to all other dogs. So these Labradors are much more food motivated because the satiety signal doesn't work quite well. And that makes them very trainable. So it links up to kind of motivation and easing and learning as well. So it's really interesting. But anyway, that's a digression. Yeah, it's true that they always eat like it's their last meal. Many dogs are like that. Yeah, they very, not mine. But that's that's like, I think, to prevent other dogs from eating their food. Anyway, there's a lot of a little bit about chemistry. I might lose you in, but let me tell you because I think it's important. And so there are melanocortin four receptors on neurons in the power of ventricular hypothalamus. They integrate these neuropeptide signals. So neuropeptides are the POMC and the AGRP, right? So AGRP axons release release what's called neuropeptide Y. And it lowers cyclic AMP and POMC axons release alpha melanostide stimulating hormone alpha MSH to increase cyclic AMP. Okay. And these two peptides, the neuropeptide Y and alpha MSH, they compete to control cyclic AMP levels. And so the neuropeptide signaling is blunted by high alpha MSH when you're satiated. And then alpha MSH signaling is blunted by high NPY when you're hungry. So that's kind of the push pull outcome of the, the, the, the, the Grayland and the leptins and so forth, right? So POMC neurons, they suppress feeding and increase energy expenditure. And they're activated by energy sufficiency signals. And the food perception can affect hepatic metabolism by melanocortin release from these POMC neurons via a nerve signal. Now, now here, many people might get this glucagon like peptide one, GLP one is made by intestinal L cells. It reduces food intake by binding GLP one receptors on AGRP and POMC neurons, right? Well, obviously these things are made in a stomach, a grilling in the stomach and GLP one in the intestine, they make their way to the brain, obviously, kind of like a whole mode, basically. So GLP one antagonists or binders, I guess GLP one ligands are given to people to reduce fat, right? They're like, what's the name of one of them? With Zempic? Zempic as well. Yeah, it's a GLP one agonist. So it mimics the agonist, it mimics the receptor, but it doesn't, yeah. So you can take it and you'll suppress your appetite all the time, whereas the normal GLP one ligand, right, is not there all the time. So so if you activate at the same time AGRP neurons and inhibit POMC neurons, you're going to get an increase in food intake compared to when you only modulate one neuronal type and that's a bunch of experiments like chemo genetic manipulation and so forth have come to that and they you know they give all the references for that and we're just making the summary here because we each each paper would be a twin, right? All right, so if you've been listening so far and getting a homeostatic need, don't aren't the only thing that drives you to eat, right? The hedonic system, as we've said, makes you eat based on reward, no matter what your energy balance. And is it, I actually don't know whether this is true, but from the reading it sounds like OZempic and the GLP one agonist largely works on what we've been talking about, which is the homeostatic side of things. This is the one that is regulating you, not quite how much pleasure. I think that's correct, yeah, even though I don't, we'll probably talk about this soon as well, but like OZempic also makes people feel less pleasure, so it's interesting, right? It's surprisingly. Anyway, all right, so the the hedonic feeding system, the lateral hypothalamic area and it's it's regulating the dopamine system are central to this hedonic process. So the LHA, the lateral hypothalamic area, LHA, neurons in this area, the LHA, project to the VTA, which is the ventral tegmental area. And if you look at the paper, if you look at the figure, you can find out where that is. The VTA is, if you're looking at the brain from the side, it's just behind the hypothalamus, okay, and it's connected to that. Yeah, it's part of the midbrain and it's under your cerebellum, so it's somewhere it's hard to tell. In the middle of your head, in the middle, midbrain, but that's the place that is where all the dopamine cells are. So last time we talked about Parkinson's-like diseases and in Parkinson's and dopamine cells die, and VTA is just part of the cells that can't done Parkinson's. So these gabanurons in the LHA project to the VTA, and they're they inhibit, they disinhibit, and that drives food-seeking behavior and consumption of highly palatable foods, even when you don't need them, right? So these VTA dopamine neurons, they integrate oral, gastrointestinal and post-absorbed signals during eating, and that it provides a substrate for associative learning mechanisms between food or water sensory quality. So you're saying that an increase in depaminergic activity. Is that what you said? Yeah, that's right, disinhibits. Okay, it drives the learning. It's interesting because if anyone has any experience with Adderall, you would know that, and also back in the 19, I don't know, 20s, like amphetamines and dopamine-increasing drugs, so drugs that increase a dopamine tone, they are prescribed as appetite or suppressant. So it's interesting that dopamine is also used as the reward system, but they think that this is to drive the learning about the food, not necessarily the the eating of the food. Also, I think there's a distinction there. Yeah, and I think to follow up on that, you know, what dopamine is going to do in one part of the brain compared to what it's going to do in like, in immediately, neighboring brain region, it should be different. Sure. And yeah, there's a lot. So I guess it's hard to, it's hard to be like dopamine or like, we should say this for most neurotransmitters, that it's like, you can't just be like, this neurotransmitter leads to, leads to x, or leads to y, it's all about like, where is it, you know, how many receptors, you know, lots of stuff like that. So it is complicated. It's very, what's the word, context dependent, brain region dependent. It's granular. But maybe to like quickly, like expand on what the role of dopamine that they are talking about in this paper. And I think that is, if anyone's following along, I mean, this is open access. So you can definitely feel free to follow along. I think this is maybe figure three. Sorry, no, figure four. So the role of dopamine, the authors, I think the field is hypothesizing, is to drive learning so that you can associate environmental stimuli to the pleasure of eating so that you can load up on food. So for example, so in the paper, they show, they measure dopamine release to stimulus, a neutral stimulus, for example, let's say a bell. So when you, normally, when you ring the bell, the animal might not do anything, they might not respond to the bell. But if you pair the bell ringing to food many, many times, the animal would start salivating to the bell. So this is Pavlov's favorite famous experiment. And when you measure dopamine, what you'll find is that at the beginning, before pairing the bell to the food, dopamine is largely released, triggered by licking and eating of the food. But as you start pairing the bell with the food, this dopamine signal graduates shifts towards the bells because the bell is predicting the food. So the role of the dopamine and in fact, and the dog starts salivating not to the food, but also to the bell. So the idea is that you start learning, so for example, in human case, like when you see, I don't know, the golden arches, you start salivating because you know that is, you know, associated with a big Mac. And stuff like, I mean, advertisers know everything about this. That's why Coca-Cola, things like that. So, and also even certain smell of food, you might need a little bit of association. So for a case in Pondurian, if you've eaten it many times and you think it tastes good, then there's horrible smell would switch in your brain to think it's good smell. And you guys also talk about cheese. I think some people, and the same with coffee, which is a bitter terrible medicine unless you've drunk a lot of it. So there's a lot of smell that, when first exposed, doesn't smell very good. It smells like feet, but when you ease it a few times, it tastes wonderful. And it smells like parmesan cheese. Like if you smell parmesan and you don't think about it, you're like, God, this smells like vomit. Like it smells like vomit. Oh, it's because of butyric acid, probably. Yeah. So, thanks. So the idea is that the hedonic system is to drive you to learn about all these environmental, environmental stimulus to get you know, many people think that single more scotches smell like vomit too, which is too bad. Really? Well, more for you. So, following on this, so, the site, smell or taste of desirable foods, triggers dopamine release in the nucleus accumbens, which is, go back to my, it's towards the front of the brain, right? in front of the hypothalamus, right? So dopamine gets released there and that promotes eating beyond physiological needs, right? And if you give an animal, intra-gastrically, a fat sugar solution, it increases dopamine release in overeating and it does more strongly than fat or sugar alone. So the combination, right? Fat plus sugar, as we said, those are the highly addictive foods. And if you give myself a high-fat diet, it reduces dopamine reuptake in rats. And humans dopamine receptor binding is reduced in subjects with obesity relative to controls. And if you knock down certain dopamine receptors, you get compulsive food seeking in rats. So again, dopamine is important for this kind of eating, this pleasure of seeking eating that we're talking about. There's also a population of dopamine receptor expressing the medium-spiny neurons of the nucleus accumbens. They project to the LHA, and the LHA is the, where is that? LHA hypothalamic area. Yeah, it's the lateral hypothalamus, so it's right in our hypothalamus there. Maybe interestingly, sorry to interrupt your flow, but the LHA, lateral hypothalamus area is the first region people discovered where if you electrically stimulate the mouse or the rat beginning is the rat would do nothing but press the button for more self-stimulation. So this is the area for not for food, just for the electric stimulation. In fact, it would for go food to stimulate. Interesting. And this is because of the, because the triggers dopamine release. So these neurons of the NAC, they go into the LHA and they preferentially synapse onto gabin neurons, which we said at the beginning are really important for feeding behavior. And if you, when you first feed, these cells are silent and that enables feeding. And then when they say, upon termination of the feeding bout, these neurons resume their activity. So again, idea that these are controlling feeding behavior. Just to really highlight the point, these are the D1 medium-spiny neurons that Vincent has spoken about. And they, they send dopamine. And just to call back from previous twin, these might very well be the same cell that Vivian talked about. When we talked about, when a mouse was giving another mouse CPR, when a mouse is, when there's a victim mouse that has been there. Right. And there's a victim mouse. I was, where was a victim of some scientist kind of anysatizing the mouse. The mouse has passed out. A helper mouse would come along and start dragging the tongue by a standard. And that actually requires these D1 medium-spiny neurons to be a little bit inhibited. And I don't know exactly whether it's the same cell that kind of suppresses feeding. Maybe this tells you not to go and eat that consume the mouse, doesn't mean you. I don't know. But these are the same. These might, they are, they are talking about the similar population of cell in the striatum. And so if you, if this, this, this connection, the NAC LHA, if you stimulate that, a mouse will stop feeding immediately, even if it's hungry. If you stimulate that axis. And then when you stop that, even if it's hungry. Yes. Even if it's hungry, and then if you stop that, feeding re-initiates. Right. Yeah. So a bunch of experiments showing that this NAC LHA protection is really important. And in fact, going back to the atrial point, if you give any drugs that increases sanatic dopamine in the striatum, they would cause these D1 medium-spiny neurons to fire. And that might be related to why humans and also rodents, experimental rodents don't eat very much when you give them a lot of dopamine. So there's the pushpull between learning about eating and the actual eating itself, perhaps. Tim, do you know, I know that the paper that you mentioned, we talked about arousal because the tongue-pulling activity, well, okay, yeah, I'd have to go back and remember in, in which, if it was the bystander or the victim mouse, the. Yeah, yeah, that's a subtlety. I can't. Do you remember which? It was the locuserulias nopinepin neurons for one of the mice, but I don't remember. Well, the locuserulias is involved in arousal, which is the point of the tongue-pulling, and I can't remember the circuit. But yeah, I'm just trying to think about how to think about the relationship between the activation of these neurons or like, modulation of these neurons, the feeling of arousal and then eating behavior. That like, if you feel. If you're highly aroused and we don't mean it in the sexual sense, we mean it in the like, you're awake, more awake, that you're maybe going to be eating less, or when you get tired, you tend to eat more, and how does that, and how does that relate to your body sensing your energy status? Because I think that's another kind of like gray area that's not really that well described, even here, which is like, how does your body. What are your energy needs? Yeah, I don't know. What event is coming up, and. Yeah, they discuss a little bit towards the end in the discussion, I guess, about like stress eating and also like night time eating disorder, someone who like a little dessert before going to bed, which is probably the worst thing you can possibly do. I think these are like concerns as well. I don't know whether people know much about the research behind it. Yeah. So there are also glutamateurgic neurons in this LHA that play a role in suppressing food intake, they have projections into the lateral habanula and the VTA, and if you ablate these LHA glutamateurgic neurons, you increase food intake, you increase body mass, and if you stimulate these LHA-gabbergic and glutamateurgic neurons, you get reward-seeking or averse of escape behaviors depending on which one you do. So these two systems, the homostatic and the hedonic system, the hedonic are not just independent things. They're working together. They give a lot of examples of how they're working together, and you can get cross-activity. And one example is depends on these POMC neurons, right? So these neurons go from the arc to the NAC, and when POMC is cleaved, guess what? It makes beta endorphin. So beta endorphin is a cleavage product of POMC, and that is the ligand of the muopioid receptor, right? That's why you feel good in certain conditions. And if you interestingly inject naloxone, which is an opioid antagonist, right? It's a drug you can give someone who is overdosing on opioids, right? That gives you evidence that of the reinforcement effects of palatable foods. And when you block these muopioid receptors, rodents consume less sweet stuff, but they eat normal quantities of chow. How cool is that, right? So they're distinguishing between different kinds of food. You know, years ago, I did some papers where if you offer mice a diet low in amino acids, they will reject it. They can sense it somehow, and it has to do with GCN 4, which is an amino acid sensing protein. Which is also present in yeast, right? But it's also a mice in that distinguish. It's very cool. It's very cool. Anyway, so there are shared circuits between these homostatic and hedonic pathways, just a little touch of that, okay? Now, there are genetic bases for overeating, right? For example, and there's a very nice box and a figure here on this. Leptin deficiency is like one in a million people worldwide, so they don't make leptin. And they're constantly hungry. Yes, yes, Tim, go ahead. Sorry, and you're right, they're constantly hungry. The babies are like 40 pounds, like three-year-old is like 70 pounds or something crazy. They are really huge because they have a terrible time suppressing to eat. But one of the reason why it is very rare to find them is because they also have reproductive deficits when you don't have leptin. And that's because your, I guess, evolutionary, it doesn't make any sense if you're starving to also, when you're starving, your body is just trying to shut down any energy diversion to anything that's completely non-necessary. And the last thing you want when you're starving out on the serengeti is to give birth to a baby and then have to nurse it. So you just shut it down. Same for the immune system, so I think leptin deficiency is associated with immunodeficiency as well. And this is just all to keep your brain going so you can look for the next meal. Yeah, sorry, that was a slightly off-topic thing. No, it's totally okay. So these kids can eat up the 6,000 K cows a day, right? So normally, what? A couple thousand is normal. That's like three marathons. So you can see, you know, like those cross-cross-fit athletes, that's how much the belly like that much. You know, these two ladies are working out like three times a day. These two ladies that just rode across the Pacific, I don't know if you heard about that. They had to consume 5,000 K cows a day and they said it was really hard to eat that much. Oh, there's a rowing constantly, right? That's incredible. You can row across the Pacific. Yeah, they did. They did two women. Cool. All right, so you can treat this leptin deficiency with recombinant leptin, right? But you have to take it for life and there are other side effects and you can get leptin resistant. So it's not ideal to do that. So the deficiency, so the question is, how does this work, right? So it can lead to overeating by the altered control of B and C two neurons onto AGRP neurons. And if you delete the leptin receptor in these neurons, the mice overeating become obese. So that's the target in those neurons themselves. And you can also see similar conditions in the POMC system where deficiency of POMC leads to overeating. The absence of alpha MSH reduces the occupancy of the ligand on downstream receptors. And altered melanocortin signaling can happen because of mutations in MC4R gene. It's another cause of another monogenic cause of overeating. But how common is that stuff? They don't save for MC4R at all. But maybe it's in the. In figure three, they plot you the relative allele frequency for these. Oh yeah, these will turn like mutation, whatever you want to call it. And it's like 10 to the minus 6, so 1 in a million. Yes. Because it's it's evolutionarily so selected again, so I think. So is a nice figure of three where they have the allele frequency versus the per allele effect size. So they have homeostatic mutations that affect homeostatic regulatory mechanisms like leptin, POMC, and MC4R. And they have little pictures of overweight babies and young kids. And then they have hedonic conditions which are multi-genic. And we'll talk about that in just a moment. But I wanted to just say that if you. So GLP 1 now, back glucocon-like peptide 1, is made by intestinal cells, like we said. It reduces food intake by acting on receptors on both AGRP and POMC neurons. Those are in the hypothalamus, right? And probably other regions as well. So that's pretty interesting. I was just going to ask. So you were talking about leptin resistance and we've all heard of insulin resistance. And this happens. The idea of resistance is when the receptor that the ligand, the hormone binds to, it's numbers. It's like presence on the target cells go down. And I was just wondering if there's any indication. There are any. I don't know, Tim, if you know. Is there any indication out there that the continued GLP 1 use is going to impact the expression of the receptor such that the people would become like GLP 1 resistance? Yeah, because a lot of systems, there's, you know, like with neurotransmitters, the like the selective serotonin reuptake inhibitors, the antidepressants, one of their functions is. one of the mechanisms, maybe the primary mechanism has to do with negative or positive feedback on the expression of the receptors on the postsynaptic cell. So, you know, there's some kind of like set point, maybe the body's right, I mean, a set except point. And so I just wonder if like the continued use of like GLP 1 or leptin could lead to those problems. And then that person would kind of be shit out of luck. They changed other things. No idea, but based on like all other receptor ligand behavior, you would expect maybe if you are on a very high dose, there would be some desensitization, and then when you remove it, there would be a strong rebound. And that might be what people see clinically, but I have absolutely no idea. Yeah. And that also, that actually that rebound happens after when people try to lose weight by fasting, by like dramatically and very quickly reducing calorie intake, the systems are like, oh no, there's a famine. So next time food is available, we're going to stock up. And so that you have that rebound weight gain. And it's reflect, it's a manifestation of the changes that are happening in these circuits and the cells in them. Yeah. I want to talk a little bit more about genetic basis of obesity. So again, remember, there's there's monogenic where one gene affects your BMI. So they've screened people and they've found about 12 genes that when mutated can drive obesity, right? And they primarily affect the homostatic feeding circuits that we've been talking about. And these include leptin that we just talked about leptin receptor POMC and MC4R. MC4R are the most common forms of these rare monogenic forms common, but still relatively rare. But but so when it goes wrong, you have a huge effect. Yeah. So these MC4R loss of function mutations, you get child onset obesity with a BMI of 4.8 kilograms per square meter corresponding to an average body weight increase of 18 kilograms, as Tim was saying. In contrast, gain of function mutations in this gene have been linked to low BMI. You see, nature does gain a function itself as well. POMC defects also leave to overeatings because the absence of alpha, MSH reduces the occupancy of MC4R on neurons in the PVH. These are the Labradoros of the human world. And then it can be chromosomal deletions like Prader, Willy syndrome is this deletion of chromosome 15. So those are the monogenics. And then there are multiple genes mutated in what's called common obesity. It's polygenic. Hundreds of polymorphisms that each have a small effect. So for example, they did a genome-wide association study, GWAS, with 800,000 people. They had they identified many low side with her allele effects of less than 0.04 kilograms per square meter, which is less than 120 grams per person. So each gene has that much. So you have to have many of those to be obese and they've identified more than 1,500 genes. Some of them affect the mesolimpic reward system or upstream circuits like stress and anxiety systems. So those are the two kinds of. Yeah, and the polygenic tiny effect ones are so hard to study because the effect size is so small and you need such a large sample, but they add up, just like your calories, like each little bit is going to contribute a little bit, and then if you have enough of it, you're going to have a tough time controlling your eating. So yeah, it's hard to combat as well. So the sedonic system, consumption of highly palatable food without hunger, they also call it the dessert effect because like Tim said earlier, dessert is by design or highly palatable and they have a combination of sugar and fat and salt that makes them highly palatable. And you could be full and you can't resist it, right? I felt that way. I've got it. Oh my gosh, I'm so full that someone puts a crème brûlée on the tail. I could eat it because it's so good. It tastes so good and you're still very full. So the eating, this sedonic eating is driven by the pleasure you get from the food tasting. So it also is linked to cravings and emotional eating, right? You have a cake craving. And these sweet and fat nutrients activate the reward system and they promote waves of dopamine release as we've been talking about before and the effect of that. It's actually quite interesting because when you are very hungry, when you're in full starvation mode, anything tastes good, you can eat absolutely anything. Yeah, that's the test. I think that's when, but I think that's when the homeostatic system kicks in is that I would just eat anything. I'm just giving me like saltine crackers and I need tons of those. But as you start filling up and your homeostatic switch is telling you, okay, you can stop now, then the hedonic really kicks in for you to fill up that tank for the horrible winter that's coming. So they note that over time with repeated these, you know, pleasure eating, you begin to just look at the food and get a desire to eat it. And the idea is, is an idea that these are cute dopamine signals which code for food value can override fullness signals leading to continued eating. And there are some experiments that support that. So, for example, if you presenting conditions stimuli associated with food elicits feeding in animals that are otherwise sated, right? The very mention of creme bruley to Vincent. Yeah, it makes me want it. It's interesting because then if you like, you know, you're talking about somebody's mentioning a food, but it can go even deeper than that. You walk into your kitchen and like, you see your fridge and, you know, it's just like some of these triggers are, might be a much deeper and much like less obvious than we think, you know. And if so, if you need to lose weight, just move your fridge. That's what I think, I think Vincent would start, we're going to the passage where they're saying they might make a comparison between food addiction, a drug addiction and quote unquote addiction. So, that might, people have hypothesized it might be triggered by the same kind of mechanism. Yeah. But just to leave the last thing about hedonic foods, they say, not just these circuits, but there are emotional factors, stress, boredom, and other things compel people to seek comfort in food. And it's true also in animal models, desserts are associated with comfort and indulgence. They can be appealing cultural norms, market forces, right? Lots of advertising of pretty looking food. And they say in many cultures, dessert is a customary part of a meal and you may eat it out of tradition and you may not even be hungry. So they say the pervasive presence of these foods in the environment, you know, schools, workplaces everywhere else normalizes their consumption. And so there's an interplay between emotional, social, and environmental factors with these neural systems that we've been talked about to modulate this. But yeah, I mean, you know, the advertising is all about making things look delicious, right? You could just go through and stick around. It works so well. Like that sound of opening a Coke can. It works so well. Or the crunching of like a pesheda chip bag? Yeah, yeah. Hey, did you bag? Yeah. Well, for me, my favorite food pasta is silent, right? Except when you break it before you put it in a pot. Yeah, I can be any kind of audience coming murder you. So the next section they try and make it parallel between drug addiction research and overeating and obesity, right? So you know, drug addiction also involves the dopamine system, right? And that's the mechanism underlying addiction. And some drugs lead to negative reinforcement, like the same with eating and so forth, especially with opioids. And they say maybe these are some shared features with overeating. But it's probably oversimplified. And it's not clear that it's the same. There's overlap in the neuronal substrates affected in both addition, addiction and obesity. But whether overeating is an addiction and is really debated in the literature and they point that out that some papers feel it isn't. Yeah. So like when I was growing up, people try to draw the comparison much very strongly because it seems to in drug addiction, which I studied in my previous postdoc, the hypothesis is that there's a gradual switch in your brain where instead of you taking drugs because you're seeking the pleasure of it, it starts developing into a habit. So you start seeing your old friends that you hang around with, who all take drugs and you start without even thinking about it, start taking drugs because you know the same environment. And in food, similar to what Vivian was saying, at the beginning, maybe you really like those frozen Oreos that you made. So you really, you know, you take a bunch of time preparing it and you save it every bite. But after a while, you walk into the kitchen and before you know it, you open up the freezer and you have an Oreo in your mouth without even thinking. And that's the development of habit that may be share some similarity with drug addiction. But I, but apparently people have been a lot more cautious about it based on this review. So I think research is still ongoing. There's actually a nice box called food addiction, a controversial concept where they say their parallels, you know, and drug addiction is compulsive nature of the consumption of it. And whether compulsive overeating occurs due to exposure to food remains controversial. But there is a group that suggests that continued exposure to food at high caloric density may override metabolic needs and cause a loss of control, which are features of addiction. But they say the concept of food addiction is not empirically supported by neurobiological investigation. So we have to be careful about that. The last thing I wanted to talk about here was the mechanisms of obesity treatments, right? And these primarily use GLP1 receptor agonists to reduce food intake and body weight. And so they try and explain how these work, right? So this peptide GLP1 is secreted by intestinal L cells. That's the third time we've said it. And it reduces food intake by acting on central GLP1 receptors, but has a short half life, right? The stuff that you make yourself. They think it's thought that these, this GLP1 acts through neuro pathways rather than as a circulating hormone. And it influences your appetite and gastric motility by nerve circuits in the gut and sympathetic surface. And I think that's because it might not penetrate the blood brain barrier very well. That's right. That's right. So this one model, the neurons that secrete GLP1 and the helium-mediate appetite reduction by signaling to the hypothalamus through nerve fibers, right? As Tim just said. So GLP1 receptor agonists, of course, they can have longer half lives because they're different up to a week. But these have poor blood brain barrier permeability. Although having just read this seems to me that you would need to get in the brain because you could just stimulate a nerve ending in the gut, for example, but anyway. Although the one feature of the homeostatic nucleus that governs their homeostatic feeding, they are all in the hypothalamus and they're in the medial part of the hypothalamus. And those regions are somewhat special because I think the blood can be a little bit leak, the blood brain barrier is a little bit leak, so they can actually the molecules can go a little bit in exert its effect in the local region. And then those effect we get passed down to the rest of the brain. So it's also possible that the GLP1 agonists have a little bit of brain fat. In fact, they point out that multiple brain regions have GLP1 receptors, right? Including places that we've been talking about are regulating food intake. So there must be some ligand getting in there, although they say some maybe the most prominent effects of the agonists are in organs that are not in the central nervous system, but they're a devoid of a blood brain barrier and they're close to the ventricles, so it's like ARC. So we don't know. So anyway, they say, okay, so GLP1 impacts food intake by both central and peripheral mechanisms, right? And they're different populations of GLP1 receptor expressing neurons, which can either drive satiety or aversion. And so they say GLP1 signaling is important for hedonic feeding and reward processing. So what are the examples of GLP1 receptor agonists? Ozempic is one semi-glutide. Is that the same as Ozempic? Do you know? There's a different. Anyway, semi-glutide and Tursepetide. Let me look it up. They're using maybe generic names. And it doesn't say Ozempic. Yeah, it's the same thing. It's the brand. Oh, yeah, four semi-glutide. So semi-glutide is the name of the compound. And then you have Ozempic and Wigovii and Rebellsus. Yeah. And then Tursepetide or two examples. They're given subcutaneously or orally. They reduce weight by 15 to 20%. Which is a lot. Yeah. Sema-glutide or Ozempic does not pass the blood-brain barrier, but can access the brain stem, the septal nucleus and the hypothalamus via circumventricular orbit. I was going to say that earlier that those are circumventricular organs that where they have holes in the blood vessels to allow things in. They're very interesting because it's not just these food-related or eating-related things. It's also signs from the immune system, toxins, things like that. So these agonists slow gastric emptying as well, which moderates the rise in blood sugar and prolongs the feeling of fullness. Which is why people are like, "I'm going to do a liquid diet or I'm going to do a smoothie diet." And I'm like, "You know, the more liquid your food is, the more quickly leaves your stomach." And then you've got like a spike in blood sugar, and so it's really, it's just not a good idea. But there are side effects, loss of muscle mass, depression, and hedonia. Which is interesting. How does it work? I don't think people know that. And is it just anodonia in general or is it. Yeah, it doesn't say it. I think it's general. So in the way, hobbies are less fun, things like that. Yeah. They've reduced the ability to experience pleasure. It's terrible, right? I would not get pleasure out of podcasting, I guess. I mean, that's depression, right? Yeah, well, that's bad too. Yeah, I know. But I mean, they ask that. Glucogon is also made by intestinal. L-cells, pancreatic alpha cells, and neurons with a certain part of the brain. It increases glycemia. And the receptor agonists can be used together with. The glucogon receptor agonists can be used together with the GLP-1R agonists to enhance weight loss. And this is because the glucogon peripheral has peripheral lipolytic effects, which enhance fat metabolism. So it's doing two different things, right? Suppressing appetite and causing lipolysis. As in, they have some. Sometimes they're working on bimodal molecules that have both properties, which could be something in the future, right? They have a glucose dependent insulinotropic polypeptide, also called the gastric inhibitory polypeptide, GIP receptor agonists and glucogon together, which act with semaglutide to enhance weight loss. And so lots of different things being worked on here because it's a big problem, right? But also big business. Big business too. Yeah. And the last thing I wanted to mention is about the impact of food on overeating. Certain foods really impact obesity prevalence. And in fact, coming to something Tim mentioned earlier, there are great examples in the changes in the food offered in developing countries, right? Where this obesity has increased in most countries between 1992 and 2022. Obesity prevalence now outpaces the decline in underweight, particularly in countries across the care, being Polynesia, Micronesia in the Middle East. And at the other end, underweight remains prevalent in South Asia and parts of Africa. 89% of countries for women and 73% for men at higher obesity rates than underweight in 2022. So that's a double burden of being underweight and obesity continues to shift towards obesity, especially in school age children. And it's the food. They think the food may help to reduce it. So reducing sugar, sweetened beverages. You know, gee, that's what RFK Junior wants to do, right? For a year has in some experiments has reduced that. You get a reduction in BMI. So the study suggests that cutting sugar, sweetened beverages can temporarily affect weight. But it's a challenge because when you go back to your sugar, sweetened beverages, you gain your weight again. You need to somehow lose the sweet tooth. And that's a, that's a difficulty is how do you? Yeah. Yeah. Now one thing that they didn't talk about here, which I mentioned at the end is that microbiome plays a role. I was just going to say. They say the microbiome and epigenetic mark in fat cells. In other words, modification of chromatin that controls gene expression or garnering a lot of attention lately. And of course, the food you eat shapes your gut flora. And so this gut brain acts just may determine what you eat. Some people think that, you know, your gut microbiome makes you like certain kinds of chocolate because it's metabolized to make certain products. So, you know, it's a good article that we've just touched on some topics. It's open access if you should take a look at it. It's got nice figures as well. I also think for those of us who are inclined towards developmental neuroscience, there's a pretty good body of literature out there on how brain development of the feet of a fetus is influenced by the diet of the mother. And so, you know, if we have overweight moms, that can impact not necessarily to cause obesity in the offspring, but I don't know. I'm not really that familiar with the literature, but it's worth keeping in mind, too, that like if we're having this obesity epidemic now, what kind of impacts is that going to have on brain function, you know, far beyond eating behavior. Some countries don't have an obesity epidemic, right? I think I'm thinking of Japan. Yep, that's right. Yeah, but I mean, have you tasted the food like fresh fish, fresh fish forever? I mean, why don't they also have delicious, they also have other meats, but could they're also guagucobi beef? Yeah, expensive beef you can afford, but one of my favorite is Tomkatsu, right? Well, that's quite unhealthy, very unhealthy, but they serve it. But I think in Japan, well, this is one thing that I think is, well, maybe there's genetics in it, but I think behavior is also very different because in Japan, a lot of the pack, if you go to Japan, and you get a Japanese portion of food, that would be like appetizer here in America. And if you get a packet of anything to buy, like for snack, it would, it's like one quarter of the size of an American. I mean, here, when I first came to America, I was in Phoenix and the default soft drink of default soda size is infinite. It's like infinite refill, and I just couldn't believe it. So that's going to have an effect on your behavior and how much food intake you take. So yeah, but certainly the portions in Japan are smaller. But you know, I really don't understand why you'd want a lot of people do this, but you'd have soda with a meal. It's a meat, the carbonation and the sweetness ruins the meal, right? You'd rather have a neutral drink. Unless you're having a big mac and a bunch of fries, and then it just cuts through the fat in the salt too, right? Yeah, I mean, I heard that that colas have salt and sugar, so it makes you thirsty and then you can drink it. Yeah, you know what? We should just like, you know, subsist on air. It's just much easier that way. And photosynthesis. Yeah, that'd be pretty cool. I don't know. Water is a great thing to drink, especially with a particularly salty meal, right? Because you want to drink any drink a lot of water, which is good. It's good to drink lots. Yeah, but if you grow up drinking soda and sweet drink, I think that has some downstream effect. Yeah, maybe, but you know, I was a drink soda as a kid, but I haven't had a soda in 30 years. I know that it's not good, but I also don't find it appealing. If I'm really thirsty, it's not so, I think out for nothing. I don't go for soda. I mean, water is great, and it has to be, I really do like teas, right? Ice teas are good, especially like a green tea or a black tea without much sugar and sweetened at all. That's great. I think those are very good for hot days, but everybody's different. I understand that, but you have to consider what's good for you or not, right? Of course, eating soda is also wrecks your teeth, right? Because it encourages the growth of bad bacteria. I guess you just got to brush your teeth every single time. Some people do after every meal, but nobody gets time for that. I know people who bring a toothbrush to work and brush their teeth after lunch. I do that. I do that. I get yelled at. I'm trying to do that. I think it's a good idea. But if you drink soda and if there's acid in your food, then brushing teeth is probably not a good idea because you're probably brushing away a normal animal. All right. That is twin numbers. 66. You can find show notes at microbe.tv/twin. If you have any questions or comments, you can send them to [email protected]. If you enjoy these programs, we'd love your support to continue them. It's a cost of money to produce them, but we don't do ads to pay for them. We depend on you to donate because we figure if you like them, you will support it. If someone said to me years ago, if someone likes something, they will pay for it. So we don't need everyone to pay for these, but we just like donors, who particularly like it, so help us out. So you go to microbe.tv/contribute. There are a number of ways that you can help us. And we're a nonprofit microbe TV. So in the US, that would be federal US tax deductible. Tim Chong is at New York University. Thank you, Tim. Thanks Vincent. That was a very fun thing to learn about which I knew very little before coming in. Yeah, me too. Vivian Marsons down in New Orleans. Thank you Vivian. New Orleans. Yeah, thank you. That was super interesting. And I just have so many other questions and comments and all of that. It's tough to reign ourselves in. But you know, now it's 2.30 pm. I didn't eat lunch, but I'm not particularly hungry actually. That's the other thing. I was like, you know, once you kind of pass some threshold, it's like, well, I guess it's getting anything. You get over that hunger. And then I'm like, I could skip lunch, but I don't think it's a good idea to skip them. So I will go. I mean, you know, there's so much more we could say about this. The intimates and fasting people would disagree. Well, that's if they've been doing it, yeah, a lot. If your circadian rhythms are expecting you to eat and you don't, that's it going to be a different outcome than somebody who's like, I don't eat until 3 o'clock every day. Anyway, it's good to eat lots of plants and not too much, right? That's the right. The Michael Pollan or however his name book. I've been to Dracanello. You can find me at microbe.tv. You've been listening to this week in neuroscience. Thanks for joining us. We'll be back next month.