Stephen's Guyenet Explains His Disagreement with Gary Taubes | JRE Obesity Debate

Three, two, one. And we're live. All right, so to set this up, when Gary was on last, Gary Taubes, Stefan, how do I say your last name? Stefan Guinier. Guinier. Yeah. Guinier. It's like DNA. Like DNA, but with a G. Right. Got it. Okay. When you were on last, Stefan had some opposition to some of the things that you were saying. We talked about getting him on and you on together. We finally pulled it off. There was a lot of wrangling, there was a lot of back and forth and cat wrangling, but we got it. We're here. Give me your position on, this is all for folks listening, this is all about obesity and the mechanism for obesity, is that fair to say? Yeah, yeah. So essentially, the main points that we want to talk about today are- Try to keep this a fist from your face. Okay, sure. Just pull it around. What causes obesity and what causes insulin resistance, which is behind a lot of our chronic diseases that are common in society? And please give us your background. Yeah, so I have a BS in biochemistry, a PhD in neuroscience. After getting my PhD in neuroscience, I went on to study the neuroscience of obesity at the University of Washington and particularly the brain circuits that regulate body fatness. Hopefully, we'll get a chance to talk about those today. And then I went on to become a science consultant, science communicator, and write a book called The Hungry Brain that is my attempt to explain for a non-specialist audience what causes obesity. And yeah, so that's my background. Now, what is your disagreement with Gary's position? Everything. Everything? Yeah, so how about I just- Can I start by explaining- Sure, that's please do. What I believe causes obesity. I'm going to be long winded here. Is that okay? It's okay. Go right ahead. We have hours. Okay, cool. So first, a little bit of housekeeping. I'm going to be citing a lot of evidence today. And so I want- Just please bring this up to your face. Okay, sure. Just move it around. Sure, sure. Because you want to sit back. How's that? Just a day. Perfect. Beautiful. I'm going to be citing a lot of evidence today and I want people to be able to follow along at home. And so I've put many of the references that I'm going to be citing on- Just do that so it doesn't cover your face. Okay. There we go. All right. I've put a lot of the references that I'm going to be citing on my website, stephangeana.com, or if you don't feel like spelling my name, you can go to wholehealthsource.org. And I have a numbered list of topics there. And I'm going to be calling out numbers. Just scroll down to the number that I referred to and the references are all there. Second thing I want to say that I want to be really clear about today is that I'm not here to be the anti-low carb guy. I think low carb diets are a valid tool for controlling body fatness and controlling blood sugar. I'm not here to talk anybody out of being on a low carb diet. What I am here to try to talk people out of is some of the mythology that has accumulated around the low carb diet. Okay. So I want to get started with an analogy to help people understand why the brain is important in obesity. So imagine you're an alien coming down from outer space and you want to understand what's going on on earth. And you notice that on the highway, some cars are traveling faster than others. Some cars go faster, some cars go slower, and you want to figure out why. And so you go and you start studying the tires of the cars, because obviously the amount of force that is exerted by the tire onto the asphalt is the thing that determines the speed of the car. We know this, this is just physics. And so you study the tires and you study the tires and you study them and you never figure out why some cars go faster than others. Now, why is that? The reason is that you're studying the wrong part of the system. If you want to understand the, why some cars go faster than others, you have to understand the part of the system that regulates speed. And that is the person behind the wheel. And so in this analogy, the tires are fat cells and the person behind the wheel is the brain. There has been tons of research on fat cell biology, on what factors put fat in fat cells, what take it out. There's been tons and tons of research on that. And it's intuitively obvious that we should be studying that to understand obesity, right? But in fact, all of that research has yielded very little insight into why some people are fatter than others. That's because it's the wrong part of the system to study. Fat cells do not regulate the size of fat cells any more than the tires on a car regulate the speed of the car. The thing that regulates the size of fat cells is the brain. So let's talk about, first I'll give you a little framework for thinking about this. The brain evolved over about 600 million years to promote the survival and reproduction of our ancestors. And over the course of that time, we evolved all these different brain circuits that have specialized functions. They generate our hunger and our cravings and our fullness feelings. They generate our eating behavior, what and how much we eat. And they actively regulate the amount of fat on our bodies. And that's one of the things I want to talk about. And all of these circuits evolved, and these are non-conscious, by the way. So you don't decide you want to be hungry, you don't decide that you want to have a craving. These are things that bubble up from non-conscious parts of your brain that you don't control. So these circuits are calibrated to an environment of our ancestors, not the environment we're living in right now. So these circuits all evolved to function optimally in the environment of our ancestors, promote the survival and reproduction of our ancestors. So what happens when you put these brain circuits in the modern environment where you have abundant, calorie-dense, tasty foods rich in carbohydrate and fat, is these same brain circuits push us to over-consume, and they push our bodies to accumulate and hold on to fat. And then what you see as a result is the three hallmarks of obesity. First of all, the obvious, you see elevated body fat mass. Second of all, you see elevated calorie intake. People with obesity consume more calories than people who do not have obesity after correcting for height and sex and physical activity level. And third, you see that people with obesity defend their higher level of body fatness against changes. And so there's actually a regulatory change that happens. It's not conscious defense. They're not trying to remain obese. It's these body fat regulatory circuits. And this is where Gary gets it right, is that people with obesity are not just lean people who eat more calories. There's actually a change in the regulatory activity that regulates body fat in the body. And we can get back to how that happens, but I'll just leave it there for now. So up until this point, I've basically just been telling a plausible story, right? I mean, I haven't actually cited any evidence yet to support that my story is correct. And so let's get into that. Let's talk about what some of the evidence is that supports this idea that I've just laid out. So I want to start with the genetics of obesity. I think this offers some... Can I interrupt for one second? As long as it's very brief. Just a question. I still don't quite understand what the model is. I understand the dysregulation, the brain, the environment. If you don't understand the model, how about I lay out, how about I finish laying it out and then you can ask a question? Because I may answer your question over the course of continuing. So let me just finish. Okay. So now the genetics of obesity offers us a lot of insight into the biological mechanisms that drive differences in body fatness in the general population. So you get these studies like the most interesting studies are the genome-wide association studies. They get hundreds of thousands of people together and they sequence or they measure all these markers in their genomes and they figure out what parts of the genome make some people fatter than others. So if you have version A in this particular location, you end up a little fatter than if you have version B. And when you look at all the places where this is happening, you can see the genes where it's happening in and that tells you, if you look at what those genes are doing, that tells you what the mechanisms are that underlie everyday differences in body fatness in the general population. And so to kind of warm ourselves up, let's start by talking about height genes. So height has a strong genetic component, so does body fatness. And researchers have figured out a lot of the genes that underlie differences in height between people. And when you look at what those genes do, they tend to be involved in the growth and development of the skeleton and the connective tissue, which is what you would expect, right? Because growth of the skeleton determines your height. So genes that determine diabetes risk, type 2 diabetes, are all about insulin sensitivity, all about insulin secretion, and the function of the insulin secreting pancreas, which is what you expect because diabetes is a disease that is all about insulin. So these studies are really good at getting at the underlying biological mechanisms that are driving these phenomena. So what do these studies have to say about obesity? If Gary's model is correct, we should see a bunch of genes popping up related to fat cells and insulin. If my model is correct, we should see a bunch of genes popping up related to the brain. And in fact, that's exactly what we see. The genetics of obesity are overwhelmingly related to differences in brain activity between individuals. And okay, so that's one piece of evidence. Another piece of evidence, there are five FDA approved weight loss drugs. Four of those act in the brain. One of them reduces dietary fat absorption in the digestive tract. There are no effective fat loss drugs that I'm aware of that target insulin or fat cells. Third piece of evidence, if you look at, some people get really unlucky in life and they end up with these horrible genetic mutations that, you know, knock out some biological pathways. Some of these people end up with extreme obesity, people and also animals. We see this in mice and rats just occasionally you get unlucky and you get really, really fat. And researchers have been cataloging what are these mutations when we find people who are genetically really obese? What are these mutations that are making them fat? What is the biological mechanism that's getting screwed up that's making them fat? And what they've found is that all of these mutations that they've identified to date, a number of them are occurring in the leptin signaling pathway. And this is the leptin, is the primary fat regulating hormone in the body. Gary avoids this, never talks about this in his writing, but leptin is the primary fat regulating hormone in the body. And these mutations either knock out leptin, they knock out leptin receptors, or they knock out the leptin response pathway in the brain. And so that's the third piece of evidence. Okay. So now we haven't really gotten around to talking about what it is exactly about the bad interaction that happens between our ancient brains and the modern food environment that causes us to become fat. We've established that the brain is central to obesity, but we haven't really established what it is exactly about that interaction. Why does our modern food, why does our modern environment promote obesity? Right? So basically there are three different ways that I'm going to look at this from, but first I want to say that the, probably the best way to answer this question is to start with the question, what is the most fattening diet in the world? What is the diet that is more fattening than any others? And the answer to that is it's human junk food in a variety of non-human species and humans, it's human junk food that is more fattening than any others. And I'm going to skip over some of the research here that demonstrates this. By the way, I haven't been calling out numbers here. Okay, let me call out some numbers. Reference number two on my website is those genetic studies. Reference number one is the obesity drugs. Reference number six is those spontaneously occurring genetic mutations. And now I'm talking about reference number 52. So I'm going to gloss over some of the individual research because I'm being long-winded here, but essentially what you find is that this stuff is really fattening in animals, many different species. It's super fattening in humans, calorie dense. When you put, create an environment with abundant, easy, calorie dense, tasty foods, rich carbs and fat, you see this dramatic over consumption and fat gain across many species, including humans. And what you find in the research is that the sugar and the carbohydrate cannot explain that. They're part of the effect. Yes, they explain part of it, but you cannot replicate that effect by only feeding sugar and carbohydrate. You can't replicate it in animals. You can't replicate it in humans. Well, when you say you can't replicate it, you mean you can't replicate obesity? What do you mean? Yeah, that's right. You cannot cause the same degree of fat gain, the same extent of fat gain, the same extent of overconsumption using only sugar and carbohydrate that you can cause with a variety of calorie dense, palatable human foods. You can't fully replicate it with sugar and carbs. You cannot fully replicate it with fat alone either. If you put those, we can get deeper in this if you want. But I'm confused. So you're saying that the diet that causes the most obesity is what we think, right? This human junk food diet, rich in sugar, simple carbs, bullshit diet, right? You're saying that you can't replicate that with just sugar and carbs? You cannot fully replicate it. Fully in one sense. What I mean is that if you just feed, if you just increase sugar intake in animals or in humans, you do get weight gain, but it is modest compared to what you get when you put people around a variety of calorie dense, palatable foods, rich in carbohydrate and fat. Similarly, if you- That's very confusing. How's that? Because I'm not sure exactly what you're saying. You're saying if you give people this calorie rich sugar diet of junk food, you will make them gain weight, but not as much weight as what? So what I'm saying is that if you give people or animals the actual human junk food with all the carbs and fat and everything, they gain a lot more weight and a lot faster than if you just give them a diet that's high in sugar and high in refined carbohydrate. And what that shows is that the sugar and the refined carbohydrate cannot fully explain the effect, can't fully explain why those foods are fattening. See this is what I'm confused. You see what I'm saying? No, I don't see what you're saying. Okay. Because you're saying if you give people the diet of American junk food, you'd get not as much of an effect if you give them just the sugar and the carbohydrates. Correct. Is that what you're saying? Yep. But what are you giving them when you're giving them the diet of junk food? You're giving them sugar and carbs. Well, for example, in animals, no, it's different because if you think about human junk foods, generally those foods contain fat and carbohydrate and salt and all kinds of other things. So it's more than just- Well, it's a lot of soda too, right? There's no sugar. Yeah. So just- It's just sugar in that. So I'll get into more detail. So the ways that you can do this, you can add sugar, just sugar, table sugar to the feed of animals. That's one way to do it. Or you can add it to their drinking water. Sometimes it's a little bit fattening. Sometimes it's not that fattening in animals. In humans, you can ask them to drink sugar, sweetened beverages that are just sugar, and you can see what happens. And people will gain weight. Or you can tell them to stop drinking sugar, sweetened beverages, and you can see what happens. Okay. People will gain weight. They will lose weight, suggesting that that is part of the explanation, but it's a much smaller effect than you see with this full palette of these foods that contain carbs and fat and all of this other stuff. So you're saying, obviously there's more calories, right? If there's carbs and fat and all these other things? Correct. If you think that calories matter, then we agree. Oh, for sure. It matters, right? Gary doesn't think it matters. You don't think it matters? I think it's the wrong way to think about it.