Stephan Guyenet on "What causes obesity?"

Rationally Speaking | Official Podcast of New York City Skeptics - Current Episodes - RS 189 - Stephan Guyenet on "What causes obesity?"

"'If we look at the history of calorie intake and calorie expenditure in this country, what we see is that, for most of the last hundred years, people have been able to roughly match calorie expenditure with an appropriate calorie intake. If you look at calorie intake a hundred years ago, it was actually pretty high. It was almost as high as it is today, and yet, there was very little obesity.

Presumably, that's because almost everyone was working manual labor jobs, we barely had any automobiles, there weren't washing machines, there weren't automatic dryers. We're doing a lot of things that required physical effort, building things in factories, milking the cows, weeding fields. What you see over the course of the next 40 or 50 years in the United States is that our calorie intake actually declined'...

'Obesity really has two fundamental characteristics and this is something that's been pointed out by my mentor, Mike Schwartz, at the University of Washington. That is, first of all, it developed due to this imbalance between intake and expenditure -- but the second is that you actually have a change in how the brain regulates body fatness and how the brain regulates the amount of energy that is coming in. Essentially the brain, instead of defending a lean state, it begins to defend an obese state against changes... That's why weight loss is so hard, is that once your brain is defending that high level of body fatness, if you try to lose weight, your brain is like, "No, this is not what I want to do."...

[On the Biggest Loser] Researchers had actually followed up on the people who lost these massive amounts of weight, 100+ pounds on The Biggest Loser and they tend to regain most, if not all, of that weight in fairly short order after the show.That's not really what you would expect if body weight were not regulated. If there was not some change that occurred or some difference in the way that these things are regulated, between someone who's obese and someone who's lean, because they're gaining weight at a much faster rate than you would expect for someone who started off at that lower body weight. Someone who starts off lean and tries to stay lean, it's going to be a lot easier than someone who starts off obese, becomes lean and tries to stay there...

There's a lot of evidence independent of that, that there is this regulation of body fat levels that does regulate around a specific preferred level. There's a researcher named Rudy Leibel, for example, who's done a lot of this work. If you take people who are either lean or obese, basically the same either way, and you get them to weight reduce by 10%, you see very profound changes in their physiology and their brain response to food cues. What you'll find is that they will have a decrease in their metabolic rate that is disproportionate to the amount of weight that they lost.It's not just because their bodies are smaller but there's actually this starvation response that kicks in that actually conserves energy even beyond that, to try to regain the lost fat.

That also has neurobiological correlates, where you can put people in an fMRI machine and you see that, basically, all of the brain structures that are responsible for making us crave food light up like a Christmas tree after the weight loss.Also, you find that when you give them food, the same amount of food is less satiating after they have lost weight. We know a lot about the mechanisms underlying this. This is why I'm so confident about this, is that we actually have a really good picture of how this works.

It relates to a hormone called leptin that's produced by fat tissue and that is a signal to the brain of how much fat is in your body. When a person loses weight, their leptin goes way down and that's really the key signal to the brain that causes that so-called starvation response that tries to bring the body fat back. The reason we know that that's key signal is that if you replace leptin back up to the pre-weight loss level, you don't get those responses..

When leptin was first discovered, it was thought of as this incredible potential miracle weight loss drug. It was very clear that it played a really important role in body fat regulation. There's almost a century of research leading up to the discovery of leptin.Basically, when you just take people who are overweight or obese and you inject leptin into them, it doesn't really do anything. It doesn't cause them to lose weight. What they figured out is these people already have high-levels of leptin, and increasing those levels further, in other words telling the brain, "Well, actually you have even more fat," doesn't really tell the brain to eat less. The brain is really responsive to decreases of leptin as a starvation signal, but is not really responsive to increases of leptin as an excess signal'...

'It's not about causing weight loss, it would be about keeping weight off'...

'There was actually this inflammatory process occurring in the hypothalamus which is the part of the brain that regulates body fat and receives that leptin signal.It turns out, from other groups as well, that this is part of a generalized stress response that occurs in the hypothalamus of animals that are becoming obese. There's increasing evidence that it actually plays a causal role. If you can prevent that inflammation from happening in the hypothalamus and these other associated stress response changes, you can actually attenuate the fat gain that occurs in experimental models of dietary obesity.We actually were able to extend that into humans...

People who have obesity actually have MRI signals in their hypothalamus that look a lot like they are also inflamed. The more signal you have in your hypothalamus that looks like inflammation, the higher your body fat in this level is likely to be.'...

'If you look at animal models of obesity, the absolute most fattening thing you can possibly give to a rodent, for example, is to give them a variety of highly palatable human junk foods. Human junk food is insanely fattening to just about any species... You actually see, also, calorie expenditure effects. What I mean by that is, at least, in certain contexts, what you'll see is that they actually burn less energy than they should on those diets. It's not quite that simple in rodents.Although in humans, you really see a lot of more effects on the energy-in side than on the energy-out side. People who have obesity have a higher level of calorie expenditure, a higher metabolic rate than people who are not obese.'...

'The difficulty with the calories out argument is that people who have obesity almost invariably have higher calorie expenditure, not a lower calorie expenditure. You can't really explain obesity by saying they have a reduced calorie expenditure because they don't, they have a higher calorie expenditure. The only way you can really explain it thermodynamically is by saying the calorie intake is higher so then, the question becomes why is the calorie intake higher.'...

As far as we currently know, if you really look at the most tightly controlled studies available in humans, of which there are a number, as far as we currently know, the calorie value of food is the only food property that meaningfully impacts body fatness. There are a number of studies that have varied other things like the carbohydrate to fat ratio, varied things like sugar intake, even varied protein. There are many, many other hypotheses that you could test about how food compositions affects body fatness that haven't been tested yet.But in terms of the basics like macro-nutrients, it doesn't have any effect. It's independent of calories, is what current evidence suggests. And so we don't really have any evidence, right now, that things other than the calorie value of food impacts that food's effect on your body fat. We do actually have pretty good evidence that the macro-nutrient composition -- that is the fat, carbohydrate and protein composition -- does not affect body fatness independently of calories...

We had these animals that their "preferred weight" or defended body weight is dependent on which diet they were on, not how many calories they're currently eating. If you take those animals that have gained a bunch of weight from eating these really awesome, calorie dense, delicious food and you switch them back to a healthy diet, a lower calorie density, unrefined diet, they will spontaneously lose weight even if you let them eat as much as they want. Their set point actually changes. It can actually go back down even if it had gone up.

And I think you see the same thing in people. Not everyone who diets does so by forcing themselves to eat smaller portions. Sometimes, when people change their diets in ways that are qualitatively better, like going from a refined calorie dense, junk food diet to a lower calorie density, healthy diet that's fresh vegetables and meats and fruits and whole grains and potatoes and things, you will see that people will spontaneously lose weight. Their appetite will spontaneously decrease... What people tend to do when they go on really bland, repetitive diets, they don't feel as hungry, they don't eat as much...

They had another group of people that they asked to lose the same amount of weight over the same period of time by just applying portion control to their habitual diet. It's like, you're going to eat the same foods you always eat, you're just going to eat less of it to match this weight loss curve of this other group.What they found is that the group that lost weight by portion control was ravenous. They had very, very different responses. They reported in the study that the people were very uncomfortable, they were dreaming of food. I'm not going to go into it because it would take a long time to explain, but they had some more physiological measures of hunger drive.

Basically, what they found was that people who lost weight on the bland diet weren't any more hungry at the end. People who lost weight by portion control were super hungry, and their food motivation kicked in so that starvation response was activated in one case but not the other, presumably because the set point had changed...

'There are a lot of randomized controlled trials that have compared low carbohydrate to low fat diets. Generally, the low carbohydrate diets cause more weight loss, although they both cause weight loss.But when you really start to dig in to those studies, the answer becomes less obvious than it seems on the surface. The reason is that if you really look at the low fat diets that are typically used as a comparator, they're really, really wimpy low fat diets...

They're not very low in fat, first of all. They're usually not as low in fat as the low carb diet is low in carbs. Second of all, they tend to be based on this antiquated concept of low fat diets, where only the low fat matters and you don't care about any other aspects of quality'

'People often replace the fat with sugar to make it taste good.'...

'Focusing on diet quality, I should say, gives you better effectiveness to not caring. You get better weight loss... the quality aspect matters independently of the macro-nutrient aspect... By quality, I'm talking about the degree to which a diet is refined junkie food.'

More evidence against the insulin-carbohydrate hypothesis of obesity