Good Calories, Bad Calories (68 page)

as a regulator of hunger and ingestive behavior.

Once human-obesity research became the domain of psychologists and psychiatrists in the 1960s, studies of hypothalamic obesity left behind once and for al the greater context of homeostasis and the use and storage of metabolic fuels, and focused instead on how Brobeck’s dual centers of the hypothalamus al egedly regulate eating behavior. This served to further the conviction that defects in this region of the brain cause overeating, and overeating causes obesity. Hunger, and the overeating that accompanies it, would be considered exclusively a psychological phenomenon, not a physiological one. (Because these psychologists would consider eating behavior to be the subject of their research, they would often screen their animals after surgery and those that didn’t eat voraciously would be “discarded.” They would then omit these animals from their subsequent analyses, even if the discarded animals became obese as wel .) Hunger was something that occurred only in the head, and so it could be decoupled from the needs of the body, at least with sufficient wil power.

Animal research continued to confirm Ranson’s hypothesis, even though its author had died, no matter whether the fattening was induced by hypothalamic lesions, genetic defects, or as the natural y occurring seasonal weight gain of hibernators. In 1946, for example, the Johns Hopkins physiologist Chandler Brooks reported that his albino mice become “definitely obese” after VMH lesions, and that they gained six times as much weight per calorie of food consumed as normal mice. In other words, it wasn’t how much these mice ate that determined their ultimate weight, or the number of calories, but how these calories were utilized. They were turned into fat, not used for fuel.

Though Brooks reported that he could prevent his albino mice from growing obese, he could do so only by imposing “severe and permanent” food restriction. If he subjected them to “long continued limitation of food,” the animals would lose some weight, but they would never lose the drive to fatten or the hunger that went with it. Periods of fasting, Brooks noted, were “fol owed by an augmentation of appetite and development of a greater degree of obesity than had been attained before fasting.” And so Brooks’s lesioned mice, as Hilde Bruch might have noted, were acting exactly like normal healthy humans and obese humans after a semi-starvation diet. These VMH lesions also resulted in changes in the reproductive cycles of the animals, and in their normal nocturnal eating patterns, which Ranson and Hetherington had also reported; once the animals became obese, they slept more than normal animals, al of which suggested that the VMH lesions had profound effects on the entire homeostatic system and could not be written off as simply affecting hunger and thus food intake.

When physiologists began studying animal hibernation in the 1960s, they again demonstrated this decoupling of food intake from weight gain.

Hibernating ground squirrels wil double their body weight in late summer, in preparation for the winter-long hibernation. But these squirrels wil get just as fat even when kept in the laboratory and not al owed to eat any more in August and September than they did in April. The seasonal fat deposition is genetical y programmed—the animals wil accomplish their task whether food is abundant or not. If they didn’t, a single bad summer could wipe out the species.

This same decoupling of food intake and weight would also be demonstrated when researchers studied what are now known as dietary models of obesity. Certain strains of rats wil grow obese on very high-fat diets, and others on high-sugar diets. In both cases, the animals wil get fatter even if they don’t consume any more calories than do lean controls eating their usual lab chow. This same decoupling occurs in animals that are regaining weight after lengthy periods of fasting. “It doesn’t matter how long you food-deprive the animal,” said Irving Faust, who did this work in the 1970s; “the recovery of body weight is not connected to the amount of food eaten during the recovery phase.” And this same decoupling of calories and weight has also been made consistently, if not universal y, in the recent research on transgenic animals, in which specific genes are manipulated.

What may have been the most enlightening animal experiments were carried out in the 1970s by physiologists studying weight regulation and reproduction. In these experiments, the researchers removed the ovaries from female rats. This procedure effectively serves to shut down production of the female sex hormone estrogen (technical y estradiol). Without estrogen, the rats eat voraciously, dramatical y decrease physical activity, and quickly grow obese. When the estrogen is replaced by infusing the hormone back into these rats, they lose the excess weight and return to their usual patterns of eating and activity. The critical point is that when researchers remove the ovaries from these rats, but restrict their diets to only what they were eating before the surgery, the rats become just as obese, just as quickly; the number of calories consumed makes little difference.

George Wade, the University of Massachusetts biologist who did much of this research, described it as a “revelation” that obesity could be brought on without overeating, just as Pennington had described it as revelatory that weight could be lost without undereating. “If you keep the animals’ food intake constant and manipulate the sex hormones, you stil get substantial changes in body weight and fat content,” Wade said. Another consequence of removing the ovaries was that the rats hoarded more food in their cages, which is analogous to storing excess calories as fat. Infusing estrogen back into these rats suppressed the food-hoarding, just as it prompted weight loss. “The animals overeat and get fat,” said Tim Bartness, who worked on this research as part of his doctoral studies with Wade in the 1970s, “but they are overeating because they’re socking al the calories away into adipose tissue and they can’t get to those calories. They’re not getting fat because they’re overeating; they’re overeating because they’re getting fat. It’s not a trivial difference. The causality is quite different.”

One critical idea here is that survival of a species is dependent on successful reproduction, and that in turn depends first and foremost on the availability of food. Fat accumulation, energy balance, and reproduction are al intimately linked, and al regulated by the hypothalamus. This is why food deprivation suppresses ovulation, and why the same kind of hormonal control of reproduction ensures that herbivores, such as sheep, tend to give birth in the springtime, when food is available. The link between food availability and reproduction was something that Charles Darwin had also observed: “Hard living…retards the period at which animals conceive,” he wrote.

The lesson of these animal experiments is that understanding energy balance and weight control requires Claude Bernard’s harmonic-ensemble perspective of homeostasis: an appreciation of the entire organism and the entire homeostatic web of hormonal regulation. “Fertility is linked to food supply, physical exercise involved in foraging for food and avoiding predators, and energy expenditure associated with temperature regulation and other physiological processes,” Wade explains. These functions are control ed by a tight orchestration of both sex hormones and those hormones that control the “partitioning and utilization of metabolic fuels,” and this is accomplished in ways that are “reciprocal, redundant and ubiquitous.”

The idea that obesity in humans is caused, as it is in animals, by a defect in the homeostatic maintenance of energy distribution and fat metabolism—that we overeat because we’re getting fat, and not vice versa—barely survived into the second half of the twentieth century, although the evidence has always supported it.

This homeostatic hypothesis effectively vanished from the mainstream thinking on human (as opposed to animal) obesity with the coming of World War I . The war destroyed the German and Austrian community of clinical investigators, who had done the most perceptive thinking about the causes of obesity and had a tradition of rigorous scientific research dating back two hundred years. In the United States, it resulted in a suspension of obesity research that lasted for most of a decade. Meanwhile, Stephen Ranson had died, Hugo Rony and Julius Bauer retired. The generation of physiologists who had founded the field of nutrition in the United States and actual y studied human metabolism disappeared with them. Francis Benedict’s Nutrition Laboratory at the Carnegie Institution did contract work for the armed services during the war and then was shut down in 1946. The Russel Sage Institute of Pathology, where Graham Lusk and Eugene Du Bois did their research, was also gone by the 1950s. Lusk himself died in 1932, Francis Benedict retired in 1937. Du Bois retired four years later.

Among the few investigators whose careers spanned the war years, Louis Newburgh was the most influential and conspicuous. As late as 1948, Newburgh was stil promoting his perverted-appetite hypothesis of obesity. The first obesity textbook published after the war, Obesity… (1949), by Edward Rynearson and Clifford Gastineau, would be considered the standard text on obesity for twenty years. It faithful y communicated Newburgh’s belief that obesity is caused by overeating. Any suggestion to the contrary, wrote Rynearson and Gastineau, constituted little more than “an excuse for avoidance of the necessary corrective measures.”

An entire generation of young researchers and clinicians effectively started the study of obesity from scratch after the war. They did so with little concern for whatever understanding had been achieved before they arrived, and so they embraced a hypothesis of causation that flew in the face of much of the evidence. The institutionalized skepticism and meticulous attention to experimental detail that are necessary to do good science—“being ruthless in self-criticism and…taking pains in verifying facts,” as the Nobel laureate chemist Hans Krebs said—had also been left behind.

THE CARBOHYDRATE HYPOTHESIS, II: INSULIN

Every woman knows that carbohydrate is fattening.

REGINALD PASSMORE AND YOLA SWINDELLS, British Journal of Nutrition, 1963

The fact that insulin increases the formation of fat has been obvious ever since the first emaciated dog or diabetic patient demonstrated a fine pad of adipose tissue, made as a result of treatment with the hormone.

REGINALD HAIST AND CHARLES BEST, The Physiological Basis of Medical Practice, 1966

IN 1929, WHEN LOUIS NEWBURGH FIRST rejected the possibility of an “endocrine abnormality” as the cause of obesity, and insisted instead that al fat people had a perverted appetite, hormones were stil widely known as “internal secretions” and endocrine glands as “ductless glands.” The first purification of growth hormone had been only nine years earlier, the purification of insulin only eight years before. In 1955, when The Journal of the American Medical Association declared unconditional y that those “theories that attributed obesity to an endocrine disturbance have been shown to be erroneous,” it was five years before Rosalyn Yalow and Solomon Berson would publish the details of the first method for measuring the insulin level in the blood, and a few more years after that before the ensuing revelations that obesity was associated with the endocrine disturbances and abnormalities of hyperinsulinemia and insulin resistance.

In other words, the editors at JAMA—and the clinical investigators they represented—were declaring that hormones, as a rule, play little role in the genesis of obesity, even before the relevant hormones could be measured accurately in the human bloodstream. In fact, it’s hard to imagine, as Julius Bauer noted, that hormones wouldn’t play a role. Here again we have that familiar scenario we first discussed with regard to dietary fat and heart disease.

Once the “truth” has been declared, even if it’s based on incomplete evidence, the overwhelming tendency is to interpret al future observations in support of that preconception. Those who know what the answer is lack the motivation to continue looking for it. Entire fields of science may then be ignored, on the assumption that they can’t possibly be relevant.

In 1968, Jean Mayer pointed out that obesity researchers may have “eliminated” hormones “from legitimate consideration” as a cause of obesity, or so they believed, but the evidence continued to accumulate just the same. Researchers had demonstrated that insulin seemed to have a dramatic effect on hunger, that insulin was the primary regulator of fat deposition in the adipose tissue, and that obese patients had chronical y high levels of insulin. Other hormones, such as adrenaline, had been shown to increase the mobilization of fat from the fat cel s. “It is probable that different concentrations of these hormones in blood are characteristic of different body types and fat contents,” Mayer wrote.

At the beginning of this century, when hormones were first discovered, it was commonly believed that obesity would be found to be due to the absolute excess or deficiency of a single hormone. When this was found to be almost never true, the popular medical position swung to the other extreme: “obesity is almost never due to hormonal disturbances; it is almost always due to overeating.” Actual y, the reasonable position ought to be:

“in order to be obese, you always have to eat more than you expend for a certain period. How often this is due to a slight shift of relative or absolute hormone concentrations, each one of which is in the ‘normal’ range, we don’t know.”

Among the hormones that play a role in regulating fat metabolism and thus potential y play a causative role in obesity, insulin was always an obvious choice. Some failure in what clinicians a century ago cal ed the insular*108 apparatus of the pancreas is the fundamental defect in diabetes, and diabetes is intimately associated with obesity in those who develop the disease as adults, and with emaciation, which was the end stage of the disease in the pre-insulin era. In 1905, Carl von Noorden invoked this intimate association between diabetes and weight to formulate the third of his speculative hypotheses of obesity, what he cal ed diabetogenous obesity. His ideas were remarkably prescient. They received little attention because insulin had not yet been discovered, let alone the technology to measure it.