TWiN 66: Neuroscience of overeating

From Microbe TV, this is Twin, This Week in Neuroscience, episode number 66, recorded on November 17th, 2025.

I'm Vincent Racaniello, and you're listening to the podcast all about the nervous system. Joining me today from New York, Tim Chung. Hello. Hi, everyone. Good to be back in this bitterly cold, not bitterly cold, fairly cold day. Winter's coming, which is a little scary. It is. Finally, it's on its way. Yeah. 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 snowed? Oh, yeah. It was snowing down Texas. I did not know this. I forgot. Well, Texas is 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 snowstorm. Like, it was like a foot of snow.

and do like in england whenever it snows snow so rarely in england that whenever it snows the whole country shuts down like even if it's like an inch of snow is that also the same in new orleans yeah okay Yeah, but it's basically like a flood, right? It's just frozen water, and we flood all the time. Yeah. I wanted to say something, but now I've forgotten it.

What did it have to do with? 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, you 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, it's not really conducive.

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. And as I 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 don't know, 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, that happens. In fact, now I just remembered what I wanted to say. 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. As you get older, the memories fade.

And it's maybe, I mean, there are hypotheses 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... Because each time you go through it, 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 retrieve it.

person as opposed to just completely blanking as you see someone who are you 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 L.A. yesterday. I went to a David Baltimore memorial. And, you know, there's a screen in front and there's 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 was 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. He tells you how to have memory and how to live longer and how to see farther and all that stuff. And this is what we do. We tell you there's nothing you can do. It's just genetics. There's nothing you can do. I'm joking. 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 for papers. Don't even draw. I'm sorry. Don't even draw that.

Well, we're different because we do papers and we don't do woo-woo science. But there are 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 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 was scrolling through my RSS feeds. 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 Schwitzgabel, and Christian Lücher. Who are, let's see, at the University of Washington, which is in Seattle. They're 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 Lake 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 two years ago. That's where my parents live. And you go from Geneva. You pass through Lausanne. Really, they lived in Montreux? Yeah, they lived there. Oh, it's beautiful. They've 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? Yeah, trying to find a way to get back there. The train. And then you go back to Geneva, you get on at Montreal, you go through Lausanne and then. And on the way, you know, it's very cool. The slopes have these little private vineyards on them, right, where they make.

Little local wines that nobody will ever get outside of the region. Swiss wine? Yeah. Oh, okay. Intriguing. I don't think I've ever had Swiss wine before. Vivian looks absolutely insulted. Anyway, this is a little about... I mean, well, you know, I'm not insulted because... Are you allowed to export Swiss wine? Is it like a local... I don't know. I don't think they export it. Yeah, okay. That's why. At least in these little family vineyards.

Sorry, what about Vivian? Well, I was just going to say, this is somewhat related. You know, it's the confluence of Switzerland and the paper today is that Swiss Gruyere. The cheese was voted the best cheese in the world on the 13th of November, 2025 at the World Cheese Awards. Sorry, what cheese again? Can you say that word? Gruyere.

Gruyere? Exactly. I was like, you mean Gruyere? Gruyere, yes. Obviously, the proper pronunciation is whatever you just said. Oh, you know what'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 Gouda, right? But the train guy says, next stop, howda!

How to? Yeah, but we don't want to be those people. And I should, I'm just, this is, I shouldn't have done this. It's like, it's like, you don't want to be like, I'm going to Paris. You're going to Howda. It's like Vincent van Gogh, or however you pronounce it. If you say that in Netherlands, they would just spit in your face. How do you say Vincent van Gogh? Something like that. I'm not Swiss. 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. 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 and 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 um High-income countries. They say developing, but you're not supposed to use that anymore. High-income, middle-income, low-income. It affects all income. Actually, in fact, as the 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 worried about. 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, 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.

a 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 have to look up durian. I hear it smells terrible. It's one of my favorite foods since I'm from that area. It smells like cat poo.

I was going to say, like hard trash. No, no. Well, a cat poo on fire, maybe. It smells kind of pungent. I don't actually know what they've probably done. MS to figure out what is the aromatics that makes it 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 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 for miles to go to a durian tree when it's ripe and get it. Because the taste is... It's hard to... It's kind of like... a little bit sweet fermented cheese, perhaps, is how I would describe it. So anyway, cashews, I like cashews, but maybe I should stay away from them now. Well, I mean, nuts 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 – not natural foods, but the processed products, right? We're all here about try 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 an... After eating another, we call them, and 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.

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... their daily caloric intake by 500 kcals, 500,000, right? 500 kcals 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 caloric density, which is what we're talking about, this 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 kind of can be deadly. Anyway, so this is what they're going to talk about here, the neurobiology, the anatomy and physiology of neurosystems 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.

that control all the circuits and regions that control eating behavior. So 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. In homeostatic, you eat because you need nutrition. Right, right. They say, this is very funny. It's common sense that when you're hungry, it drives eating. And that relieves the negative state associated with hunger.

then that's it, and you stop eating. In most cases, people stop eating when they're sated. Okay, that's a word we'll use. When you're sated, when you've eaten enough, you stop eating. Yeah, feel full. Go ahead, go ahead. Yeah, you feel full. You feel full. 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. That's why dessert is at the end of a meal, not at the beginning. Because you wouldn't want it unless it were really sweet, right? Yeah. It's because 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. you probably won't want to eat after you've got yourself on a steak and like cream spinach, whatever. Someone give you like a salad or maybe even, I don't know, cheese.

A cheese board. But if someone gives you a salad, you probably won't touch it anymore. But if someone gives you a nice dessert, you will still eat it. It's interesting. The order of salads and main dishes is different in different countries. 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 creme brulee, and then I will have it because I love creme brulee. Best dessert ever. Not just sugar and fat, but also caramelization. But also most places don't have it, so it's good.

Do you have creme brulee? No. Okay, that's it. I'm done. Give me the bill. But anyway, they say overeating may be an evolutionary advantage in animals because they can store fat, right? We're tougher times. So maybe that's one of the origins. Which I think they see also in Inuit 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 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 game is not available. It would not do well as an Inuit. But like hibernating bears, and you see quite a lot of other organisms that do this. But we don't have that same kind of pressure. Because we invented farming.

Yeah, yeah. I'm reading a book called Pathogenesis, and it talks about how there's some thought that the arrival of agriculture was like the... one of the main drivers of basically the downfall. Of everything that goes wrong. Everything that goes wrong. Yes, it's like, you know, you bring people, people come together. From disease to fake news. It's all because of farming. So this is...

Hunger-driven eating and pleasure-driven eating, homeostatic 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 homeostatic system and the hedonic system. In the homeostatic, 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. Just to reiterate the point, I think the 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. 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 homeostatic feeding. And you can see that in the picture there. And, of course, that's connected to many other places 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... homeostatic feeding. The arcuate 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 paraventricular...

nucleus or the PVH. So there's a lot of abbreviations here. Hopefully we can remember them. Now in the arcuate nucleus, so these are two places that are involved in homeostatic feeding. arcuate nucleus, they're two gamma-aminobutyric acid, GABA-responsive neurons that mediate this, right? They are... Aguti-related peptides, or AGRP neurons. And these activate when you're hungry to promote feeding. And then they're the pro-opio-melanocortin, or POMC. POMC. POMC neurons.

which inhibit feeding when your energy stores are fine, right? Well done for pronunciating that. There's no way I could have done it. I know these words. 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. They call them a...

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. There are references for that.

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 I spoke to a person who worked on ghrelin. It said they had no idea it would be the stomach. They found ghrelin circulating. They had no idea that the stomach would be secreting it. Okay, so ghrelin is secreted by the stomach.

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? feel full but your stomach is empty but like i don't know how long it would take after i eat a meal like how long it takes yeah like for my stomach to be gone everything to pass down well it varies 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 uh 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, 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 start rising. Okay. So the ghrelin 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 ghrelin and inhibited by leptin.

They 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. Okay. 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 biochemically and functionally different.

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. And so I would be interested to see if there are certain fat deposits that are bigger. secretors of insulin are 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. Overeat. Yeah, that's a good question. You're getting liposuction to lose weight, but maybe the effect doesn't 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, right? And they have stem cells too.

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 I'm not an expert on this. But there are stem cells. There's stem cells. So it's like with cancer, right? Like, did you... Did you get a totally clean margin? I don't know. How plastic is adipocytes transcriptional?

Can it like de-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 de-differentiation programs that would take like a mature. adipocyte and turn it into a stem cell. But I'd have to, don't quote me on that. So these signals, ghrelin, leptin, insulin, 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 made, and they go into this quite a bit. So, 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 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 Obi-Obi mouse is kind of like a Jabba the Hutt of the mouse. completely ginormous. Related to this, I was watching a Royal Institution lecture by a guy called Dr. Giles. Yao, I think that's his name. He's from the 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 use for guide dogs are Labrador Retriever. So they are very, very nice dogs. 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're labradors and they're a little bit they're a little bit chunky

Full of chonk, as the kids call them. And the reason why, this team from University of Cambridge found out, the reason why is because these Labrador retrievers have a mutation in the POMC. G. 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 eating and learning as well. So it's really interesting. 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. Not mine. But that's, I think, to prevent other dogs from eating their food.

Anyway, there's a little bit of biochemistry I might lose you in, but let me tell you because I think it's important. So there are melanocortin-4 receptors on neurons in the paraventricular hypothalamus. integrate these neuropeptide signals. So neuropeptides are the POMC and the AGRP, right? So AGRP axons release what's called neuropeptide Y, and it lowers cyclic AMP, and POMC axons release...

alpha-melanostite-stimulating hormone, alpha-MSH, to increase cyclic AMP, okay? And these two peptides... 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 outcome of the ghrelin and the leptins and so forth.

So the POMC neurons, they suppress feeding and increase energy expenditure. And they're activated by energy sufficiency signals. And food perception can affect hepatic metabolism by melanocortin release from these POMC neurons via a nerve signal. Now, here, many people might get this.

Glucagon-like peptide 1, GLP-1, is made by intestinal L-cells. It reduces food intake by binding GLP-1 receptors on... AGRP and palm seed neurons, right? So obviously these things are made in the stomach, ghrelin in the stomach and GLP-1 in the intestine. They make their way to the brain, obviously. Kind of like a hormone, basically. So GLP-1 antagonists or binders, I guess, GLP-1 ligands. are given to people to reduce fat, right? What's the name of one of them? Ozempic?

Zempic is one. Yeah, it's a GLP-1 agonist, so it mimics it. Agonist. It mimics the receptor, but it doesn't, yeah. So you can take it and you will suppress your appetite all the time, whereas the normal GLP-1 ligand is not there all the time. 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 there's a bunch of experiments.

like chemogenetic manipulation and so forth, have come to that. And they give all the references for that. And we're just making the summary here because each paper would be a twin, right? Mm-hmm. All right. So if you've been listening so far and getting it, homeostatic needs 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. I actually don't know whether this is true, but from the reading, it sounds like Ozempic and the GLP-1 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, we'll probably talk about this as well, but Ozenpec also makes people feel less pleasure. So it's interesting, supposedly. Anyway.

All right, so the hedonic feeding system, the lateral hypothalamic area, and it's regulating the dopamine system, are central to this hedonic. 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.

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 Parkinsonism, dopamine cells die. And VTA is part of the cells that can die in Parkinson's.

So these GABA neurons in the LHA project to the VTA, and there they inhibit, they disinhibit dopamine neurons, 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 postabsorptive signals during eating.

And that provides a substrate for associative learning mechanisms between food or water sensory quality. So you're saying that an increase in dopaminergic activity. Is that what you said? Yeah, that's right. Disinhibits. Drives the learning. It's interesting because if anyone has any experience with Adderall, you would know that. I was just going to say.

Back in the 1920s, like amphetamines and dopamine increasing drugs. So drugs that increase their dopamine tone, they are prescribed as appetite 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 eating of the food.

Also, I think that'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 could be different um chill 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 that leads to x or it 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.

Yeah, it's granular. But maybe to quickly 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 in the paper, they measure dopamine release. to a stimulus, a neutral stimulus, for example, let's say a bell. So normally when you ring the bell, the animal might not do anything, 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 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 gradually shifts towards the bells because the bell is predicting the food.

so the role of the dopamine and and in fact and the dogs are 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 associated with a Big Mac. And stuff like, I mean, advertisers know everything about this. That's why Coca-Cola, things like that. And also even certain smell of food you might...

need a little bit of association. So for a casein pond, durian, if you learn, if you've eaten it many times and you think it tastes good, then this horrible smell would switch in your brain to think it's a 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 yes 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. Is it? Yeah. So the idea is that the hedonic system is to drive you to learn about all these environmental stimulus to get you to start eating.

Many people think that single 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... towards the front of the brain, right? In front of the hypothalamus, all right? So dopamine gets released there and that promotes eating beyond physiological needs, right? And if you... give an animal intragastrically a fat sugar solution, it increases dopamine release.

And it does so 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 mice a high-fat diet, it reduces... dopamine reuptake in rats. In 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 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? Lateral hypothalamic area. Yes, 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 to... for more cell stimulation. So this is the area for, not for food, just for the electric stimulation. In fact, it would forego food to stimulate. Interesting.

because it triggers dopamine release. So these neurons of the NAC, they go into the LHA and they... Preferentially synapse onto GABA neurons, which we said at the beginning are really important for feeding behavior. And 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, the idea that these are controlling feeding behavior.

Just to highlight the point, these are the D1 medium spiny neurons that Vincent are talking about, and they sense dopamine. And just to... callback 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... Yeah, right. When there's a victim mouse, that was a victim of some scientist kind of anesthetizing the mouse. The mouse has passed out. A helper mouse would come along and start dragging the tongue. Bystander. And that actually requires these D1 medium sputum 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, consume the mouse as a meal.

I don't know. But these are the same cell. They are talking about the similar population of cell in the striatum. And so if you... The NAC, LHA. If you stimulate that, they say 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 reinitiates, right? Yeah. So a bunch of experiments showing that this NAC-LHA protection are really important. In fact, going back to the Adderall point, if you give any... drugs that increases cyanotic 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 push-pull 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 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 leucous earliest norepinephrine neurons for one of the mice, but I can't remember.

Well, so the locus coeruleus 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 activate modulation of these neurons, the feeling of arousal and then eating behavior.

that like if you feel if you know if you're highly aroused and we don't mean it in the sexual sense we mean it in the like you are right you're yeah you're awake more awake um That you're maybe going to be eating less or when you get tired, you tend to eat more. 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 like what is your uh your what are your energy needs Yeah, I don't know. It has to do with what event is coming up. Yeah, they discuss a little bit towards the end. discussion i guess about like stress eating and also like nighttime eating disorder as someone who'd like a little dessert before going to bed um which is probably the worst thing you can possibly do um i think you

I think these are concerns as well. I don't know whether people know much about the research behind it. So there are also glutamatergic neurons in this LHA that play a role in... suppressing food intake. They have projections into the lateral herbenula and the VTA. And if you ablate these LHA glutamatergic neurons, you increase food intake, you increase body mass.

And if you stimulate these LHA, GABAergic and glutamatergic neurons, you get reward-seeking or aversive escape behaviors, depending on which one you do.

So these two systems, the homeostatic and the hedonic systems, 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 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 mu opioid receptor, right?

It's why you feel good. There are certain conditions. And if you intracerebrally inject naloxone, which is an opioid antagonist. It's a drug you can give someone who is overdosing on opioids. That gives you evidence of the reinforcement effects of palatable foods. And when you block these mu opioid 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 GCN4, which is an amino acid-sensing protein, which is also present in yeast, right? But it's also a mice, and that distinguishes it. It's very cool.

Anyway, so there are shared circuits between these homeostatic and hedonic pathways. Just a little touch of that. Now, there are genetic... basis 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.

Constantly hungry. 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... They have a terrible time suppressing to eat. But one of the reasons 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 you're, I guess, evolutionary. It doesn't make any sense if you're starving.

When you're starving, your body is trying to shut down any energy diversion to anything that's completely not 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. And same for the immune system. So I think leptin deficient 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 to 6,000 kcals a day, right? So normally what? A couple thousand is normal. That's like three marathons. Is it like two marathons? I don't even know. Yeah, you know like those CrossFit athletes? That's how much they'll eat that much. These people are working out like three times a day. These two ladies that...

that just rode across the Pacific. I don't know if you heard about that. They had to consume 5,000 kcals a day, and they said it was really hard to eat that much. Oh. Because they're 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?

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 altered control of BNC2 neurons onto AGRP neurons. And if you delete the leptin receptor in these neurons, mice overeat and 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.

Altered melanocortin signaling can happen because of mutations in MC4R gene. It's another monogenic cause of overeating. How common is that stuff? They don't say for MC4R at all. In figure three, they plot you the relative allele frequency for these alternate, like mutation, whatever you want to call it. And it's like 10 to the minus six, so one in a million.

Yes. Because it's evolutionarily so selected against, I think. So it's 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 multigenic, and we'll talk about that in just a moment. But I wanted to just say that...

So GLP-1 now, glucagon-like peptide 1, is made by intestinal L 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. Yeah. So that's pretty interesting. Go ahead. I was just going to ask. So you were talking about leptin resistance and we've all heard of insulin resistance. And this.

The idea of resistance is when the receptor that the ligand, the hormone, binds to, its numbers, its presence on the target cells go down. And I was just wondering if... Is there any indication out there that the continued GLP-1 use is going to impact the expression of GLP-1? of the receptor such that the people would become like a GLP one, uh, resistant. Oh, yeah, because because a lot of systems there's, you know, like with neurotransmitters, the like, like.

the selective serotonin reuptake inhibitors, the antidepressants, one of their functions is, or like the, one of the mechanisms, maybe the primary mechanism has to do with kind of with, uh, like. 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 that like the body's... Right, homeostatic set 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 unless 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 you 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 you have that rebound weight gain. And 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 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. They primarily affect the homeostatic 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. Still rare. But when it goes wrong, you have a huge effect. Yeah, so these MC4 are 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 in itself as well. POMC defects also lead to overeatings. because the absence of alpha-MSH reduces the occupancy of MC4R on neurons in the PVH. These are the Labradors in human world. That's right. And then there can be chromosomal deletions, like Prater-Willi syndrome is a 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 identified many loci with parallel 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 Mesolympic. a reward system or upstream circuits like stress and anxiety systems. So those are the two kinds of… 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. 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 pseudonic system, consumption of highly palatable food without hunger, they also call it the dessert effect. Because like Tim said earlier, desserts by design are 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.

I felt that way. I've got, oh my gosh, I'm so full. Then someone puts a creme brulee 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 hedonic eating is driven by the pleasure you get. from the food tasting. It also is linked to cravings and emotional eating, right? You have a 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. Like you can eat absolutely anything. That's the test. I'm hungry.

But I think that's when the homeostatic system kicks in. I would just eat anything. Just give me saltine crackers and I'd eat tons of those. But as you start filling up and you're 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 for the horrible winter that's coming so they they note that over time with repeated these

you know, pleasure eating, you begin to just look at the food and get the desire to eat it. And the idea is, is an idea that... These are cued 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're presenting conditioned stimuli.

associated with food elicits feeding in animals that are otherwise sated. The very mention of creme brulee to Vincent. Yeah, it makes me want it, yeah. 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 might be a much deeper, much less obvious than we think.

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 might make a complaint.

comparison between food addiction a drug addiction and quote-unquote food addiction yeah so that might people have hypothesized it might be triggered by the same kind of mechanism yeah But just to leave, last thing about hedonic food, 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. 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 talking about to modulate this. But yeah, I mean, you know, the advertising is all about... making things look delicious, right? You can just go through Instagram. It works so well, like that sound of opening a Coke can. It works so well. The crunching of like a potato chip bag. Yeah, yeah. Yeah, crisps. Potato chip bag, yeah.

For me, my favorite food, pasta, is silent, right? Don't make any sound, but it's delicious. Except when you break it before you put it in a pot. And then Italians come and 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 addiction and obesity. But whether overeating is...

And addiction is really debated in the literature, and they point that out, that some papers feel it is. Yeah, like when I was growing up, people... try to draw the comparison very strongly because it seems so in drug addiction, which I studied in my previous postdoc, the hypothesis is that the... 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're in 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 take a bunch of time preparing it and you save 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 a development of habit that maybe share some similarity with drug addiction. But apparently people have been a lot more cautious about it based on this review. So I think research is still ongoing to drive a parallel. There's actually a nice box called Food Addiction, a Controversial Contract.

concept where they say they're 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 treatment, right? And these primarily use GLP-1 receptor agonists to reduce food intake and body weight. And so they try and explain how these work, right? So this peptide, GLP-1, is secreted by intestinal L cells. That's the third time we've said it. And it reduces. Food intake by acting on central GLP-1 receptors. But it has a short half-life, right? The stuff that you make yourself. They think it's thought that these...

This GLP-1 acts through neural 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… GLP-1 and the ileum mediate appetite reduction by signaling to the hypothalamus through nerve fibers, right, as Tim just said.

So GLP-1 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... It seems to me that you wouldn't 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 the 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 leaky. The blood-brain barrier is a little bit leaky there. So they can actually...

The molecules can go a little bit in, exert its effect in the local region, and then those effects will get passed down to the rest of the brain. So it's also possible that the GLP-1 agonist can have a little bit of brain effect. In fact, they point out that multiple brain regions have... GLP-1 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 maybe the most prominent effects of the...

Agonists are in organs that are not in the central nervous system, but they're devoid of a blood-brain barrier, and they're close to the ventricles, like ARC. So we don't know. So anyway, they say, okay, so GLP-1 impacts food intake by both central and peripheral mechanisms, right? There are different populations of GLP-1 receptor-expressing neurons, which can either drive satiety or aversion.

They say GLP-1 signaling is important for hedonic feeding and reward processing. So what are the examples of GLP-1 receptor agonists? Ozempic is one. Semaglutide. Is that the same as Ozempic? Do you know? Or is it different? Anyway, semaglutide and terzepatide. Let me look it up. Semaglutide. They're using maybe... Generic names. Hmm. It doesn't say. Yeah, it's the same thing. It's the brand name for semaglutide. Different brand. So semaglutide is the…

is the name of the compound. And then you have Ozempic and Wegovi and Ribelsus. Yeah. And then Terzepatide. They're two examples. They're given subcutaneously or orally. They reduce weight by 15 to 20 percent. Which is a lot. Semaglutide or mozempic does not pass the blood-brain barrier but can access the brain stem, the septal nucleus.

And the hypothalamus via circumventricular organs. I was going to say that earlier, that those are circumventricular organs where they have holes in the blood vessels to allow things in. They're very, very interesting because it's not just these, you know, 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, you know, 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 it leaves your stomach. You already processed it. And then you've got like a... bike in blood sugar yeah you know 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. And is it like just anhedonia like in general or is it? No, it doesn't say here. I think it's general. So like in the way... Like hobbies. Hobbies are less fun. Things like that. Weird. Yeah. They reduce the ability to experience pleasure. It's terrible, right? Mm-hmm. 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.

It's also made by intestinal L cells, pancreatic alpha cells, and neurons within a certain part of the brain. It increases glycemia. And the receptor agonist can be used together with the glucagon receptor. agonists can be used together with the GLP-1R agonists to enhance weight loss. And this is because the glucagon peripheral... has peripheral lipolytic effects, which enhance fat metabolism. So it's doing two different things, right? Suppressing appetite and causing lipolysis.

They're working on bimodal molecules that have both properties, which could be something in the future. They have a glucose-dependent insulinotropic polypeptide. also called the gastric inhibitory polypeptide, GIP receptor agonists, and glucagon 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. 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 Caribbean, Polynesia, Micronesia, and 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 had higher obesity rates than underweight in 2022. So that's a double burden of being underweight in 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 Jr. wants to do, right? for a year 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. Yeah. You need to somehow lose the sweet tooth, and 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 are garnering a lot of attention lately. And of course, the food you eat shapes your gut flora. And so this gut-brain axis 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 and so forth. So it was really interesting. So, you know, it's a good article. We've just touched on some topics. It's open access. 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 if we're having this obesity epidemic now, what kind of impact is that going to have on brain function far beyond eating behavior?

Some countries don't have an obesity epidemic, right? I'm thinking of Japan. Yep, that's right. Yeah, but I mean, have you tasted the food? Like fresh fish?

Fresh fish forever? That sounds delicious. They have meats, but... Wagyu Kobe beef. Yeah, expensive beef you can't afford. But one of my favorite is tonkatsu, right? Well, that's quite unhealthy. Deep fried. Very unhealthy, but they... 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, 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's like one quarter the size of an American I mean here when I first came to America I was in Phoenix and the default soft drink, the 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.

Yeah, but certainly the portions in Japan are smaller. Yeah. 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. To me, 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. And the salt too, right? Yeah. I mean, I heard that colas have salt and sugar, so it makes you...

Thirsty, and then you keep drinking it. Yeah, you know what? We should just 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 and you 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 drank 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 soda you go for. I don't go for soda. I mean, water is great, and it has to be... I really do like teas, right? Iced teas are good, especially...

like a green tea or a black tea without much sugar in it or unsweetened 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 sodas also wrecks your teeth, right? Because that encourages the growth of bad bacteria. I guess you just got to brush your teeth every single time. Some people do after every meal. Ain't nobody got time for that.

I know people who bring a toothbrush to work and brush their teeth after lunch. I do that. I do that. You 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 enamel, animal, whatever it's called. Enamel. Yeah.

All right, that is twin number 66. You can find show notes at microbe.tv slash twin. If you have any questions or comments, you can send them to twin at microbe.tv. And if you enjoy these programs, We'd love your support to continue them. It costs 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. As someone said to me years ago, if someone likes...

something they will pay for it. We don't need everyone to pay for these, but we just like donors who particularly like it to help us out. You go to microbe.tv slash contribute. There are a number of ways. that you can help us. And we're a nonprofit, MicrobTV. So in the U.S., that would be federal U.S. tax deductible. Tim Chung 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 Morrison's down in New Orleans. Thank you, Vivian. Yeah, thank you. That was super interesting. I just have so many other questions and comments and all of that. It's tough to rein ourselves in.

But, you know, now it's 2.30 p.m. 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, your body's like, well, I guess. It's totally correct. 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 a meal. So I will go. I mean, you know.

There's so much more we could say about this. The intermittent fasting people would disagree. Yeah. Well, that's if they've been doing it a lot. If your circadian rhythms are expecting you to eat. And you don't, that's going to be a different outcome than somebody who's like, I don't eat until three o'clock every day.

Anyway, it's good to eat lots of plants and not too much, right? Right. The Michael Pollan, or however you say his name, book. I'm Vincent Draconello. 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.