Good Calories, Bad Calories

The alternative hypothesis, that the obesity in these animals was a disorder of fat metabolism, came from Ranson and Hetherington. Whereas Brobeck interpreted his argument in the context of Newburgh’s beliefs, Ranson interpreted his from the context of thirty years of brain research. Some of the lesioned animals ate voraciously, Ranson noted, which might have been due to hunger alone, but others ate normally and still grew obese. (Several of Brobeck’s rats also grew obese while eating no more than lean rats did, but Brobeck dismissed their relevance to his overeating hypothesis on the basis that some other effect “related to the feeding habits” of these animals might be responsible.^*107 ) Ranson also noted “the tremendously decreased activity of these obese rats.”

Ranson argued that Brobeck’s hyperphagia hypothesis missed the bigger picture. “Insistence upon the primary importance” of either overeating or inactivity “would in all probability represent oversimplification of the problem, and this for at least two reasons,” Ranson wrote.

In the first place, the two factors are complementary in their effect upon body weight. Both would tend to increase it. A very sedentary life, combined with a high caloric intake would seem to be an ideal combination for building up a thick panniculus adiposus [layer of fat]. Secondly, these two factors may be only symptomatic, and not fundamental. It is not difficult to imagine, for example, a condition of hidden cellular semistarvation caused by a lack of easily utilizable energy-producing material, which would soon tend to force the body either to increase its general food intake or to cut down its energy expenditure, or both.

Damage to the ventromedial hypothalamus caused a defect that directed nutrients away from the tissues and organs where they were needed for fuel and into the fat tissue, Ranson argued. It made the animals more lipophilic. This reduced the supply of fuel to the other cells of the body and so caused “hidden cellular semistarvation,” or what Astwood later called “internal starvation.” That in turn led to the voracious hunger—hyperphagia—that Brobeck had considered the primary defect. As long as nutrients continued to be channeled into fat and away from the cells of other tissues and organs, the animals would remain hungry. If they couldn’t satisfy this hunger by eating more—when their food supply was restricted, for instance—they would respond by expending less energy.

Brobeck’s scenario—that the primary role of the ventromedial hypothalamus is to regulate food intake—would survive into the modern era of obesity research, but Ranson’s insights were far more profound. Only Ranson could explain all the observations, and he did so based on an ongoing revolution in the understanding of the brain, and particularly the role of the hypothalamus. This was Ranson’s expertise. The hypothalamus is the “concertmaster” of homeostasis, as Time wrote in 1940, reporting on a two-day conference dedicated to discussing the “orchestral effects” of the hypothalamus and paying tribute to Ranson, who had done much of the research.

Just before Ranson and Hetherington took to inducing corpulence in rats, Ranson had studied the hypothalamic regulation of fluid balance. This influenced his interpretation of the later research. Our bodies conserve fluids and water, just as they do fuel. Even our saliva and gastric juices are reabsorbed and reused. Just as damage to the ventromedial hypothalamus can induce obesity, damage elsewhere in the hypothalamus can induce diabetes insipidus. The symptoms of this rare condition are excessive urination and a tremendous and constant thirst. These symptoms appear in uncontrolled diabetes mellitus as well, but in diabetes insipidus, insulin secretion is not impaired, so blood sugar and fat metabolism remain regulated and no sugar appears in the urine.

The similarities between diabetes mellitus and diabetes insipidus had led Ranson and other physiologists to conclude that the homeostatic regulation of fluid balance was akin to that of blood sugar. That both diabetes insipidus and obesity could be caused by hypothalamic lesions informed Ranson’s interpretation of the underlying disorders. In the case of diabetes insipidus, the lesions inhibit the ability of the kidneys to conserve water by suppressing the secretion of an anti-diuretic hormone that normally works in the healthy animal to inhibit urination. This failure in the homeostatic regulation of fluids causes the kidney to excrete too much water, and that leads to a compensatory thirst to replace the fluid that’s lost.