Good Calories, Bad Calories

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 (technically estradiol). Without estrogen, the rats eat voraciously, dramatically 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 still 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 all 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 all intimately linked, and all 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 controlled 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 II. 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 actually 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 Russell 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.