The likely explanation is the effect of diet on this regulation of fat metabolism and energy balance. Since insulin, as Astwood noted, is the hormone responsible for promoting the incorporation of fat into our adipose tissue and the conversion of carbohydrates into fat, the obvious suspects are refined carbohydrates and easily digestible starches, which have well-documented effects on insulin. This is what Peter Cleave argued, albeit without understanding the underlying hormonal mechanisms at work, and what the geneticist James Neel, father of the thrifty-gene hypothesis, came to believe as well. And it’s the effect of these carbohydrates on insulin that would explain the dietary observations—the futility of calorie restriction, the relative ease of weight loss when carbohydrates are restricted, and perhaps two centuries of anecdotal observations that sweets, starches, bread, and beer are uniquely fattening.

In this hypothesis, obesity is another variation on the theme of insulin dysfunction and diabetes. In Type 1 diabetes, the cause is a lack of insulin. The result is an inability to use glucose for fuel and to retain fat in the fat tissue, leading to internal starvation, as Astwood put it, excessive hunger, and weight loss. In obesity, the cause is an excess of insulin or an inordinate sensitivity to insulin by the fat cells; the result is an overstock of fuel in the adipose tissue and so, once again, internal starvation. But now the symptoms are weight gain and hunger. In obesity, the weight gain occurs with or without satisfying the hunger; in Type 1 diabetes, the weight loss occurs irrespective of the food consumed.

This alternative hypothesis of obesity ultimately vanished in the 1980s, a casualty of the official consensus that fat was the dietary evil and carbohydrates were the cure. Ironically, it disappeared just as all the relevant physiological mechanisms had been worked out and a causal path established from the carbohydrates in the diet through insulin to the regulatory enzymes and molecular receptors in the adipose tissue itself.

This alternative hypothesis of obesity constitutes three distinct propositions. First, as I’ve said, is the basic proposition that obesity is caused by a regulatory defect in fat metabolism, and so a defect in the distribution of energy rather than an imbalance of intake and expenditure. The second is that insulin plays the primary role in this fattening process, and the compensatory behaviors of hunger and lethargy. The third is that carbohydrates, and particularly refined carbohydrates—and perhaps the fructose content as well, and thus the amount of sugars consumed—are the prime suspects in the chronic elevation of insulin; hence, they are the ultimate cause of common obesity. These latter two propositions—that insulin regulates fat deposition and carbohydrates regulate insulin—have never been controversial, but they’ve been dismissed as irrelevant to obesity, given the ubiquitous belief that obesity is caused by overeating. That, I will argue, was a mistake.