Good Calories, Bad Calories

The study of human obesity, however, has included only a few vague conceptions of the physiological underpinnings of hunger and satiety. One common assumption is that when the stomach is empty it contracts, and that signals hunger. By this logic, dietary fat contributes to satiety by prolonging the drainage of nutrients out of the stomach. Another assumption is that hunger is a sensation that exists in the brain, having little or nothing to do with the immediate metabolic needs of the body itself. Though many obesity researchers will reflexively disagree with this statement, it is essential to the conventional wisdom—that the ability to remain indefinitely on a calorie-restricted diet is a matter of willpower, and the failure to remain on such a diet is a failure of character. Once the pursuit of a therapy for obesity left physiology and biochemistry behind and became a subdiscipline of psychology and psychiatry, and once it was “established” that the only way to lose weight, as Melvin Konner suggested, is to grow accustomed to feeling hungry, the natural focus of virtually all obesity research became, and has remained, the brain.

By the early 1970s, a handful of hypotheses had been proposed to explain how the brain might induce hunger and satiety, and in turn regulate weight by limiting caloric consumption to match expenditure. Two received the most attention and have entered the textbooks as the most likely explanations. Both hypotheses date to the 1950s; neither took into account the evolving research on insulin, insulin resistance, and fat metabolism. Both had conspicuous deficiencies that would be overlooked.

One is Jean Mayer’s glucostat hypothesis or, technically, the glucostatic regulation of food intake, and it is invoked to explain the short-term initiation of meals. Receptors in the hypothalamus, said Mayer, metabolize glucose, initiating the sensation of hunger when the available supply of glucose falls, and provoking satiety when it rises. This glucostatic regulation, as Mayer put it, is an “essential component of the mechanism by which the needs of the body make themselves felt in the satiety centers.” It couldn’t be the only one, however, because it offered no explanation for what Mayer called “the problem of the nature of the very fine adjustment knob…the mechanism which will make you regain the weight you lost after an illness, and which makes so difficult the maintenance of weight loss after an arduous weight reduction course.”

The second hypothesis, what the Cambridge University physiologist Gordon Kennedy called lipostatic regulation or the lipostat, would evolve in the 1970s into the remarkably durable notion that we are all endowed with a certain set point of body weight or adiposity that we defend against both caloric deprivation and (perhaps less vigorously) caloric surplus. By Kennedy’s logic, the lipostat is also located in the hypothalamus and accomplishes its fine-tuning job by monitoring the amount of fat in the body or some by-product of metabolism that is released into the bloodstream in relationship to our adiposity. When this adiposity signal dips below an acceptable level—the set point—the lipostat responds by increasing food intake or decreasing energy expenditure. When the adiposity signal moves above this set point, the lipostat works to suppress food intake and perhaps increase expenditure. According to this hypothesis, the fundamental difference between the lean and the obese is the amount of fat stores that the hypothalamus is set to defend—the set point—not the manner or vigor with which it is defended. Whatever our weight, if we find ourselves in a situation where our current level of body fat is beneath that of our set point, we will fatten easily until we’ve reached our predetermined level.

This hypothesis is a reformulation based on animal research of what had been considered a fact of life in pre–World War II nutrition textbooks, that “weight loss triggers the dual pressures of increased food intake and decreased caloric expenditure,” as Stunkard put it. Nonetheless, obesity authorities have typically considered it unacceptably nihilistic. “It is not appealing from the therapeutic point of view,” as Stunkard said, “because it sounds kind of…hopeless. If you’re fat and your set point is elevated, you’re in bad shape.” And, of course, if we’re fat, or very fat, it is difficult to argue that our set point is not elevated. Moreover, the hypothesis simply failed to explain how the brain manages to monitor our fat stores, and then raise or lower food intake and energy expenditure in response. Saying that we’re all endowed with a lipostat that monitors our adiposity and then regulates hunger appropriately is just another way of saying that our weight remains remarkably stable, whether we’re lean or obese, and then assigning the cause to a mysterious mechanism in the brain whose function is to achieve this stability.