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
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
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.
Regarding the potential dangers of sugar in the diet, it is important to keep in mind that fructose is converted more efficiently into glycerol phosphate than is glucose. This is another reason why fructose stimulates the liver so readily to convert it to triglycerides, and why fructose is considered the most lipogenic carbohydrate. Fructose, however, does not stimulate the pancreas to secrete insulin, so glucose is still needed for that purpose. This suggests that the combination of glucose and fructose—either the 50–50 mixture of table sugar (sucrose) or the 55–45 mixture of high-fructose corn syrup—stimulates fat synthesis and fixes fat in the fat tissue more than does glucose alone, which comes from the digestion of bread and starches.
It is important also to know that the fat cells of adipose tissue are “exquisitely sensitive” to insulin, far more so than other tissues in the body. This means that even low levels of insulin, far below those considered the clinical symptom of hyperinsulinemia (chronically high levels of insulin), will shut down the flow of fatty acids from the fat cells. Elevating insulin even slightly will increase the accumulation of fat in the cells. The longer insulin remains elevated, the longer the fat cells will accumulate fat, and the longer they’ll go without releasing it.
Moreover, fat cells remain sensitive to insulin long after muscle cells become resistant to it. Once muscle cells become resistant to the insulin in the bloodstream, as Yalow and Berson explained, the fat cells have to remain sensitive to provide a place to store blood sugar, which would otherwise either accumulate to toxic levels or overflow into the urine and be lost to the body. As insulin levels rise, the storage of fat in the fat cells continues, long after the muscles become resistant to taking up any more glucose. Nonetheless, the pancreas may compensate for this insulin resistance, if it can, by secreting still more insulin. This will further elevate the level of insulin in the circulation and serve to increase further the storage of fat in the fat cells and the synthesis of carbohydrates from fat. It will suppress the release of fat from the fat tissue. Under these conditions—
By the mid-1960s, four facts had been established beyond reasonable doubt: (1) carbohydrates are singularly responsible for prompting insulin secretion; (2) insulin is singularly responsible for inducing fat accumulation; (3) dietary carbohydrates are required for excess fat accumulation; and (4) both Type 2 diabetics and the obese have abnormally elevated levels of circulating insulin and a “greatly exaggerated” insulin response to carbohydrates in the diet, as was first described in 1961 by the Johns Hopkins University endocrinologists David Rabinowitz and Kenneth Zierler.
The obvious implication is that obesity and Type 2 diabetes are two sides of the same physiological coin, two consequences, occasionally concurrent, of the same underlying defects—hyperinsulinemia and insulin resistance. This was precisely what von Noorden had suggested in 1905 with his diabetogenous-obesity hypothesis, even down to the notion that obesity would naturally result when muscle tissue becomes resistant to taking up glucose from the circulation before fat tissue does. Now the science had caught up to the speculation. “We generally accept that obesity predisposes to diabetes; but does not mild diabetes predispose to obesity?” as Yalow and Berson wrote in 1965. “Since insulin is a most lipogenic agent, chronic hyperinsulinism would favor the accumulation of body fat.”
When Yalow and Berson measured individual insulin and blood-sugar responses to the consumption of carbohydrates, they reported that even lean, healthy subjects exhibit “great biologic variation” in what they called the “insulin-secretory responses.” In other words, we secrete more or less insulin in response to the same amount of carbohydrates, or our insulin is more or less effective at lowering blood sugar or at promoting fat accumulation, or it remains elevated in the circulation for longer or shorter periods of time. And because variations of less than 1
