John Brobeck, a Yale researcher who had done his Ph.D. work with Ranson, was the first to propose a mechanistic explanation for the phenomenon. Brobeck had replicated Hetherington’s experiments in his Yale laboratory and then read Newburgh’s articles arguing a perverted appetite as the cause of obesity. Now Brobeck perceived his research as providing experimental confirmation in laboratory animals of Newburgh’s hypothesis. The hypothalamic lesions, Brobeck argued, served to damage what amounted to a center of hunger regulation in the hypothalamus. The lesions made the rats hungry, and so the rats over ate and grew obese. He would later write about his astonishment at how voraciously these surgically lesioned rats ate. Because obesity in most of his rats (but not all) appeared only after the rats began eating ravenously, Brobeck reasoned incorrectly that “the laws of thermodynamics suggest that…food intake determines weight gain.” Brobeck coined the term hyperphagia to describe the extraordinary hunger manifested by these animals, and hyperphagia would become the accepted technical term for a perverted appetite that leads to obesity.

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.