The First Law
Body fat is carefully regulated, if not exquisitely
so.
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What I mean by “regulated” is that our bodies, when healthy, are working diligently to maintain a set amount of fat in our fat tissue-not too much and not too little-and that this, in turn, is used to assure a steady supply of fuel to the cells. The implication (our working assumption) is that if someone gets obese it’s because this regulation has been thrown out of whack, not that it’s ceased to exist.
The evidence that fat tissue is carefully regulated, not just a garbage can where we dump whatever calories we don’t burn, is incontrovertible.
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That obesity runs in families (we’re more likely to be fat if our parents were fat) and that the local distribution of fat itself can be a genetic attribute (the steatopygia of certain African tribes) tells us that body fat is regulated, because how else would the genes passed from generation to generation influence our fat and where we put it, if not through the hormones and enzymes and other factors that regulate it?
That the amount of fat (and even the type of fat) animals carry is carefully regulated also argues for this conclusion. We are, after all, just another species of animal. Animals in the wild may be naturally fat (hippopotami, for instance, and whales). They’ll put on fat seasonally, as insulation in preparation for the cold of winter or as fuel for annual migrations or hibernations. …But they never get obese, meaning they won’t suffer adverse health consequences from their fat the way humans do.
They won’t become diabetic, for instance. No matter how abundant their food supply, wild animals will maintain a stable weight-not too fat, not too thin-which tells us that their bodies are assuring that the amount of fat in their fat tissue always works to their advantage and never becomes a hindrance to survival. When animals do put on significant fat, that fat is always there for a very good reason. The animals will be as healthy with it as without.
Excellent examples of how carefully animals (and so presumably humans, too) regulate their fat accumulation are hibernating rodents-ground squirrels, for example, which double their weight and body fat in just a few weeks of late summer. Dissecting these squirrels at their peak weight, as one researcher described it to me, is like “opening a can of Crisco oil-enormous gobs of fat, all over the place.”
But these squirrels will accumulate this fat regardless of how much they eat, just like Wade’s ovary-less rats. **They can be housed in a laboratory and kept to a strict diet from springtime, when they awake from hibernation, through late summer, and they’ll get just as fat as squirrels allowed to eat to their hearts’ content. They’ll burn the fat through the winter and lose it at the same rate, whether they remain awake in a warm laboratory with food available or go into full hibernation, eating not a bite, and surviving solely off their fat supplies. **
The fact is, there’s very little that researchers can do to keep these animals from gaining and losing fat on schedule. Manipulating the food available, short of virtually starving them to death, is not effective. The amount of fat on these rodents at any particular time of the year is regulated entirely by biological factors, not by the food supply itself or the amount of energy required to get that food. And this makes perfect sense. If an animal that requires enormous gobs of fat for its winter fuel were to require excessive amounts of food to accumulate that fat, then one bad summer would have long ago wiped out the entire species.
**It may be true that evolution has singled out humans as the sale species on the planet whose bodies do not work to regulate fat stores carefully in response to periods of both feast and famine, that some people will stockpile so much fat merely because food is available in abundance that they become virtually immobile, but accepting this conclusion requires that we ignore virtually everything we know about evolution. **
A final argument for the careful regulation of body fat is the fact that everything else in our bodies is meticulously regulated. Why would fat be an exception? …
**The Second Law **
**Obesity can be caused by a regulatory defect so small that it would be undetectable by any technique yet invented. **
Remember the twenty-calorie-a-day problem I discussed earlier? If we overeat by just twenty calories each day-adding just 1 percent or less to our typical daily caloric quota, without a compensatory increase in expenditure-that’s enough to transform us from lean in our twenties to obese in our fifties. In the context of the calories-in/calories-out logic, this led to the obvious question: **How do any of us remain lean if it requires that we consciously balance the calories we eat to those we expend with an accuracy of better than 1 percent? That seems impossible, and assuredly is. **
Well, these same twenty calories a day is all this regulatory system has to misdirect into our fat cells to make us obese. The same arithmetic applies. If, by some unlucky combination of genes and environment, a regulatory error causes our fat cells to store an excess of just 1 percent of the calories that would otherwise be used for fuel, then we are destined to become obese.
**The Third Law **
**Whatever makes us both fatter and heavier will also make us overeat. **
This was the ultimate lesson of Wade’s rats. It may be counterintuitive, but it has to be true for every species, for every person who puts on pounds of fat. It’s arguably the one lesson we (and our health experts) have to learn in order to understand why we get fat and what to do about it.
**This law is one fact we can count on from the first law of thermodynamics, the law of energy conservation, which health experts have been so determined to misapply. **
Anything that increases its mass, for whatever reason, will take in more energy than it expends. So, if a regulatory defect makes us both fatter and heavier, it is guaranteed to make us consume more calories (and so increase our appetite) and/or expend less than would be the case if this regulation was working perfectly.
Here’s where growing children help as a metaphor to understand this cause and effect of getting fat and overeating.
…(my son) gained seventeen pounds in three years, so he certainly consumed more calories than he expended. He overate. Those excess calories were used to create all the necessary tissues and structures that a larger body needed, including, yes, even more fat.** But he didn’t grow because he consumed excess calories. He consumed those excess calories-he overate-because he was growing. **
That growth is the cause and overeating the effect is almost assuredly true for our fat tissue as well.
To paraphrase what the German internist Gustav von Bergmann said about this idea more than eighty years ago, we would never even consider the possibility that children grow taller because they eat too much and exercise too little (or that they stunt their growth by exercising too much). So why assume that these are valid explanations for growing fat (or remaining lean)? “That which the body needs to grow it always finds,” von Bergmann wTote, “and that which it needs to become fat, even if it’s ten times as much, the body will save for itself from the annual balance.”
The only reason to think that this isn’t true, that the cause and effect go in one direction when we get taller (growth causes overeating) and the other when we grow fatter (overeating causes growth),* is that this is what we grew up believing and we never stopped to consider if it actually makes sense. The far more reasonable assumption is that growth in both cases determines appetite and even energy expenditure-not the other way around. We don’t get fat because we overeat; we overeat because we’re getting fat.*
Over the past eighty years, researchers have learned that they can make rats and mice obese by breeding, by surgery (removing the ovaries, for instance), by the manipulation of their diets, and by any number of genetic manipulations. The animals on which these indignities are inflicted do indeed become obese, not just functionally fat (like blue whales or hibernating ground squirrels). They tend to suffer from the same metabolic disturbances, including diabetes, that we do when we become obese.
It doesn’t matter, though, what technique is used to make the animals obese; they’ll still get that way, or at least significantly fatter (just as Wade’s rats did), whether or not they can eat any more calories than otherwise identical animals that remain lean. They get obese not because they overeat but because the surgery or breeding or genetic manipulation or even the change in diet has disturbed the regulation of their fat tissue. They begin stockpiling calories as fat, and then their bodies have to compensate: they eat more, if possible; they expend less energy if not. Often they do both.
Take, for example, the preferred method of making laboratory rodents obese from the 1930S through the 1960s. This was a surgical technique that required inserting a needle into a part of the brain known as the hypothalamus, which controls (not coincidentally) hormone secretion throughout the body. After the surgery, some of these rodents would eat voraciously and get obese; some would become sedentary and get obese; some would do both and get obese.
The obvious conclusion, suggested first by the neuroanatomist Stephen Ranson, whose Northwestern University laboratory pioneered these experiments in the 1930S, is that the surgery has the direct effect of increasing body fat on these rodents. After the surgery, their fat tissue sucks up calories to make more fat; this leaves insufficient fuel for the rest of the body-what Ranson called “hidden semi-cellular starvation”-and “force[s] the body either to increase its general food intake or to cut down its expenditure, or both.”
The only way to prevent these animals from getting obese is to starve them-to inflict what a Johns Hopkins University physiologist in the 1940S called “severe and permanent” food restriction. If these animals are allowed to eat even moderate amounts of food, they end up obese.** In other words, they get fat not by overeating but by eating at all.** Even though the surgery is in the brain, it has the effect of fundamentally **altering the regulation of body fat, not appetite. **
The same thing holds true for animals that are bred to be obese, for which obesity is in their genes In the 1950s, Jean Mayer studied one such strain of obese mice in his Harvard laboratory. As he reported it, he could get their weight below that of lean mice if he starved them sufficiently, but they’d “still contain more fat than the normal ones, while their muscles have melted away.” Once again, eating too much wasn’t the problem; these mice, as Mayer wrote, “will make fat out of their food under the most unlikely circumstances, even when half starved.”
Then there are Zucker rats. Researchers began studying these rats in the 1960s, and they are still a favorite obesity model today. These rats, like Mayer’s mice, are genetically predisposed to get fat. When Zucker rats are put on a calorie-restricted diet from the moment they’re weaned from their mothers’ milk, they don’t end up leaner than their littermates who are allowed to eat as much as they want. They end up fatter.
They may weigh a little less, but they have just as much or even more body fat. Even if they want to be gluttons, which they assuredly do, they can’t, **and they still get even fatter **than they would have had they never been put on a diet. On the other hand, their muscles and organs, including their brains and kidneys, are smaller than they’d otherwise be. Just as the muscles in Mayer’s mice “melted away” when starved, the muscles and organs in these semi-starved Zucker rats are “significantly reduced” in size compared with those fat littermates who get to eat freely. “In order to develop this obese body composition in the face of calorie restriction,” wrote the researcher who reported this observation in 1981, “several developing organ systems in the obese rats [are] compromised.”
Let’s think about this for a second. If a baby rat that is genetically programmed to become obese is put on a diet from the moment it’s weaned, so it can eat no more than a lean rat would eat, if that, and can never eat as much as it would like, it responds by compromising its organs and muscles to satisfy its genetic drive to grow fat. It’s not just using the energy it would normally expend in day-to-day activity to grow fat; it’s taking the materials and the energy it would normally dedicate to building its muscles, organs, and even its brain and using that.
When these obese rodents are starved to death-an experiment that fortunately not too many researchers have done-a common result reported in the literature is that the animals die with much of their fat tissue intact. In fact, they’ll often die with more body fat than lean animals have when the lean ones are eating as much as they like. As animals starve, and the same is true of humans, they consume their muscles for fuel, and that includes, eventually, the heart muscle. **As adults, these obese animals are willing to compromise their organs, even their hearts and their lives, to preserve their fat. **
The message of eighty years of research on obese animals is simple and unconditional and worth restating: obesity does not come about because gluttony and sloth make it so; only a change in the regulation of the fat tissue makes a lean animal obese.
The amount of body fat on obese animals is determined by a balance of all the various forces that work on the fat tissue-on the fat cells, as we’ll see-either to put fat in or to get fat out. Whatever has been done to these animals to make them fat (surgery, genetic manipulation), the effect is literally to change this balance of forces so that the animals increase their fat stores. Now “eating too much” is a meaningless concept, because otherwise normal amounts of food are now “too much.” The fat tissue is not reacting to how much these animals are eating but only to the forces making them accumulate fat. And because increasing body fat requires energy and nutrients that are needed elsewhere in their bodies, they will eat more if they can. If they can’t-if they are on a strict diet-they will expend less energy, because they have less to expend. They may even compromise their brains, muscles, and other organs. Half-starve these animals and they’ll still find a way to stockpile calories as fat, **because that’s what their fat tissue is now programmed to do. **
If this is true of humans, and there’s little reason to think it’s not, it is the explanation for the paradigm-challenging observation I mentioned earlier, regarding extremely poor but overweight mothers with thin, stunted children. Both mother and children are, indeed, half-starved. The emaciated children, their growth stunted, respond as we’d expect. **The mothers, however, have fat tissue that has developed its own agenda (we’ll see shortly how this can happen). It will accumulate excess fat, and does so, even though the mothers themselves, like their children, are barely getting enough food to survive. They must be expending less energy to compensate.
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