Good Calories, Bad Calories

That increasing the secretion of insulin can in fact cause obesity (i.e., excess fat accumulation) would be demonstrated conclusively in animal models of obesity, particularly in the line of research we discussed in Chapter 21 on rats and mice with lesions in the area of the brain known as the ventromedial hypothalamus, or VMH. In the 1960s, this research became another beneficiary of Yalow and Berson’s new technology to measure circulating levels of insulin. As investigators now reported, insulin secretion in VMH-lesioned animals increases dramatically within seconds of the surgery. The insulin response to eating also goes “off the scale” with the very first meal. The more insulin secreted in the days after the surgery, the greater the ensuing obesity. Obesity in these lesioned animals could be prevented by short-circuiting the exaggerated insulin response—by severing the vagus nerve, for example, that links the hypothalamus with the pancreas.^*117 Similarly, the hypersecretion of insulin was reported to be the earliest detectable abnormality in genetic strains of obesity-prone mice and rats.

By the mid-1970s, it was clear that Stephen Ranson’s insights into obesity in these animals had been confirmed. The lesion causes a defect in the part of the hypothalamus that regulates what researchers have come to call fuel partitioning—the result is the hypersecretion of insulin. The insulin forces the accumulation of fat in the fat tissue, and the animal overeats to compensate. This research refuted John Brobeck’s notion, which has since become the standard wisdom in the field, that the VMH lesion causes overeating directly and the animals grow fat simply because they eat too much. These studies were neither ambiguous nor controversial. In 1976, University of Washington investigators Stephen Woods and Dan Porte described as “overwhelming” the evidence that the increased secretion of insulin is the primary effect of VMH lesions, the driving force of obesity in these animals.

This half century of research unequivocally supported the alternative hypothesis of obesity. It established that the relevant energy balance isn’t between the calories we consume and the calories we expend, but between the calories—in the form of free fatty acids, glucose, and glycerol—passing in and out of the fat cells. If more and more fatty acids are fixed in the fat tissue than are released from it, obesity will result. And while this is happening, as Edgar Gordon observed, the energy available to the cells is reduced by the “relative unavailability of fatty acids for fuel.” The consequence will be what Stephen Ranson called semi-cellular starvation and Edwin Astwood, twenty years later, called internal starvation. And as this research had now made clear, the critical molecules determining the balance of storage and mobilization of fatty acids, of lipogenesis and lipolysis, are glucose and insulin—i.e., carbohydrates and the insulin response to those carbohydrates.

Just a few more details are necessary to understand why we get fat. The first is that the amount of glycerol phosphate available to the fat cells to accumulate fat—to bind the fatty acids together into triglycerides and lock them into the adipose tissue—also depends directly on the carbohydrates in the diet. Dietary glucose is the primary source of glycerol phosphate. The more carbohydrates consumed, the more glycerol phosphate available, and so the more fat can accumulate. For this reason alone, it may be impossible to store excess body fat without at least some carbohydrates in the diet and without the ongoing metabolism of these dietary carbohydrates to provide glucose and the necessary glycerol phosphate.

“It may be stated categorically,” the University of Wisconsin endocrinologist Edgar Gordon wrote in JAMA in 1963, “that the storage of fat, and therefore the production and maintenance of obesity, cannot take place unless glucose is being metabolized. Since glucose cannot be used by most tissues without the presence of insulin, it also may be stated categorically that obesity is impossible in the absence of adequate tissue concentrations of insulin…. Thus an abundant supply of carbohydrate food exerts a powerful influence in directing the stream of glucose metabolism into lipogenesis, whereas a relatively low carbohydrate intake tends to minimize the storage of fat.”

Forty years ago, none of this was controversial—and the facts have not changed since then. Insulin works to deposit calories as fat and to inhibit the use of that fat for fuel. Dietary carbohydrates are required to allow this fat storage to occur. Since glucose is the primary stimulator of insulin secretion, the more carbohydrates consumed—or the more refined the carbohydrates—the greater the insulin secretion, and thus the greater the accumulation of fat. “Carbohydrate is driving insulin is driving fat,” as the Harvard endocrinologist George Cahill recently summed it up.