stimulator of insulin release and synthesis.” Since insulin will “facilitate lipogenesis” and inhibit the release of fat in the adipose tissue, this in turn created what Sidbury called the “milieu for positive fat balance” in the cells of the adipose tissue. “Thus it was reasoned,” Sidbury wrote, “that a low carbohydrate diet would create the conditions vis-a-vis insulin metabolism which would decrease the constant stimulation of the [insulin-secreting] cells of the pancreas. The decreased insulin levels would then permit normal fatty acid mobilization.”
The diet that Sidbury eventually used in his clinic and claimed to be uniquely effective contained only 15 percent carbohydrates—“the remaining being apportioned approximately equally between protein and fat”—and from three to seven hundred total calories a day, depending on the child’s age. The older the child, the more calories allowed. “Many parents do not believe their child can be satisfied with so little food,” Sidbury wrote. “Their attitude changes completely,” however, when they see the “obvious change in the amount of food which satisfies the children.”*131
The phenomena of hunger and satiety have been the running subtext of all our discussions of obesity: the “persistent clamor of hunger” that attends semi-starvation diets; the absence of hunger during fasting and carbohydrate restriction; the question of whether insulin works as a fattening hormone or a hunger hormone when used to treat anorexia. And then, of course, there is the association of hunger, or at least positive caloric balance, with weight gain. If there’s one thing the law of energy conservation does indeed tell us, it’s that anything that works to increase or decrease our body mass must have compensatory effects on the balance of calories consumed and calories expended. Thus, any viable hypothesis of obesity must also be a hypothesis of hunger and satiety, and perhaps, as Alfred Pennington noted, of energy expenditure as well.
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.
The more fundamental criticism is that the concept of a set point or a lipostat has little precedent in physiology, whereas the long-term stability of body weight can be explained by a much simpler mechanism that does. Life is dependent on homeostatic systems that exhibit the same relative constancy as body weight, and none of them require a set point, like the temperature setting on a thermostat, to do so. Moreover, it is always possible to create a system that exhibits set-point-like behavior or a settling point, without actually having a set-point mechanism involved. The classic example is the water level in a lake, which might, to the naive, appear to be regulated from day to day or year to year, but is just the end result of a balance between the flow of water into the lake and the flow out. When Claude Bernard discussed the stability of the
This is where physiological psychologists provided a viable alternative hypothesis to explain both hunger and weight regulation. In effect, they rediscovered the science of how fat metabolism is regulated, but did it from an entirely different perspective, and followed the implications through to the sensations of hunger and satiety. Their hypothesis explained the relative stability of body weight, which has always been one of the outstanding paradoxes in the study of weight regulation, and even why body weight would be expected to move upward with age, or even move upward on average in a population, as the obesity epidemic suggests has been the case lately. And this hypothesis has profound implications, both clinical and theoretical, yet few investigators in the field of human obesity are even aware that it exists.
This is yet another example of how the specialization of modern research can work against scientific progress. In this case, endocrinologists studying the role of hormones in obesity, and physiological psychologists studying eating behavior, worked with the same animal models and did similar experiments, yet they published in different journals, attended different conferences, and thus had little awareness of each other’s work and results. Perhaps more important, neither discipline had any influence on the community of physicians, nutritionists, and psychologists
