Good Calories, Bad Calories

produced in the liver from the conversion of fat into ketone bodies. “He would surely have concluded that removal of the pancreas causes fatty acid metabolism to go awry,” McGarry wrote. “Extending this hypothetical scenario, the major conclusion of Banting’s work might have been that the preeminent role of insulin is in the control of fat metabolism.”

McGarry’s parable focused on diabetes, but the point he made extends to virtually everything having to with insulin. Just as diabetes has traditionally been perceived as a disorder of carbohydrate metabolism—even though fat metabolism is also dysfunctional—insulin has always been perceived as a hormone that primarily functions to regulate blood sugar, though, as we’ve discussed, it regulates the storage and use of fat and protein in the body as well. Because blood sugar could be measured easily through the first half of the twentieth century, but not yet the fats in the blood, the focus of research rested firmly on blood sugar.

From the 1920s through the 1960s, a series of discoveries in the basic science of fat metabolism led to a revolution in the understanding of the role of insulin and the regulation of fat tissue in the human body. This era began with a handful of naive assumptions: that fat tissue is relatively inert (a “garbage can,” in the words of the Swiss physiologist Bernard Jeanrenaud); that carbohydrates are the primary fuel for muscular activity (which is still commonly believed today); and that fat is used for fuel only after being converted in the liver into supposedly toxic ketone bodies. The forty years of research that followed would overturn them all—but it would have effectively no influence on the mainstream thinking about human obesity.

Those who paid attention to this research either had no influence themselves—Alfred Pennington comes to mind—or were so convinced that obesity is caused by overeating that they couldn’t imagine why the research would be relevant. From the 1950s onward, clinical investigators studying and treating obese patients, as Hilde Bruch commented, seemed singularly uninterested in this research. “Until recently, knowledge of the synthesis and oxidation of fat was quite rudimentary,” Bruch wrote in 1957. “As long as it was not known how the body builds up and breaks down its fat deposit, the ignorance was glossed over by simply stating that food taken in excess of body needs was stored and deposited in the fat cells, the way potatoes are put into a bag. Obviously, this is not so.” By 1973, after details of the regulation of fat metabolism and storage had been worked out in fine detail, Bruch found it “amazing how little of this increasing awareness…is reflected in the clinical literature on obesity.”

There are three distinct phases of the revolution that converged by the mid-1960s to overturn what Bruch called the “the time-honored assumption that fat tissue is metabolically inert,” and the accompanying conviction that fat only enters the fat tissue after a meal and only leaves it when the body is in negative energy balance.

The first phase began in the 1920s, when biochemists realized that the cells of adipose tissue have distinct structures and are not, as was previously believed, simply connective tissue stuffed with a droplet of oily fat. Researchers then demonstrated that the adipose tissue is interlaced with blood vessels such that “no marked quantity of fat cells escapes close contact with at least one capillary,” and that the fat cells and these blood vessels are regulated by “abundant” nerves running from the central nervous system.

This led to the revelation that the fat in the cells of the adipose tissue is in a continual state of flux. This was initially the work of a German biochemist, Rudolf Schoenheimer. In the early 1930s, while working at the University of Freiburg, Schoenheimer demonstrated that animals continually synthesize and degrade their own cholesterol, independent of the amount of cholesterol in the diet. After Hitler came to power in January 1933, Schoenheimer moved to New York, where he went to work at Columbia University. It was in New York that Schoenheimer collaborated on the development of a technique for measuring serum cholesterol and, by doing so, launched the medical profession’s obsession with cholesterol levels. Then, with David Rittenberg, he developed the technique to label or tag molecules with a heavy form of hydrogen known as deuterium^*111 so that their movement through the metabolic processes of the body could be followed. Schoenheimer and Rittenberg put this technique to work studying the metabolism of fat, protein, and carbohydrates in the body.

Among their discoveries is that both dietary fat and a considerable portion of the carbohydrates we consume are stored as fat—or, technically, triglycerides—in the adipose tissue before being used for fuel by the cells. These triglycerides are then continuously broken down into their component fatty acids, released into the bloodstream, moved to and from organs and tissues, regenerated, and merged with fatty acids from the diet to reform a mixture of triglycerides in the fat cells that is, as Schoenheimer put it, “indistinguishable as to their origin.” Fat stored as triglycerides in the adipose tissue, and the fatty acids and triglycerides moving through the bloodstream are both part of the same perpetual cycle of fat metabolism. “Mobilization and deposition of fat go on continuously, without regard to the nutritional state of the animal,” as the Israeli biochemist Ernst Wertheimer explained in 1948, in a seminal review of this new science of fat metabolism.^†112 “The ‘classical theory’ that fat is deposited in the adipose tissue only when given in excess of the caloric requirement has been finally disproved,” Wertheimer wrote. Fat accumulates in the adipose tissue when these forces of deposition exceed those of mobilization, he explained, and “the lowering of the fat content of the tissue during hunger is the result of mobilization exceeding deposition.”

The controlling factors in this movement of fat to and from the fat tissue have little to do with the amount of fat present in the blood, thus little to do with the quantity of calories consumed at the time. Rather, they must be controlled, Wertheimer wrote, by “a factor acting directly on the cell,” the kind of hormonal and neurological factors that Julius Bauer had discussed. Over the next decade, investigators would begin to refer to these factors that increase the synthesis of fat from carbohydrates and the deposition of fat in the adipose tissue as lipogenic, and those that induce the breakdown of fat in the adipose tissue and its subsequent release into the circulation as lipolytic.

The second phase of this revolution began in the 1930s, with the work of Hans Krebs, who showed how our cells convert nutrients in the bloodstream into usable energy. The Krebs cycle, for which Krebs shared the Nobel Prize in Medicine in 1953, is a series of chemical reactions that generate energy in the mitochondria of cells, which are those compartments commonly referred to as the “power plants” of the cells. The Krebs cycle starts with the breakdown products of fat, carbohydrates, and protein and then transforms them into a molecule known as adenosine triphosphate, or ATP, which can be thought of as a kind of “energy currency,” in that it carries energy that can be used at a later time.^*113 This cycle of reactions will generate energy whether the initial fuel is fat, carbohydrates, or protein. Indeed, Krebs had initiated his research assuming, as was common at the time, that carbohydrate was “the main energy source of muscle tissue.” But he came to realize that fat and protein also supply fuel for muscle tissue, and that there was no reason why carbohydrates should be the preferred fuel. “All three major constituents of food supply carbon atoms…for combustion,” he wrote.

By 1950, the addition of the Krebs cycle to the revelations about fat metabolism from Schoenheimer and others provided the foundation for understanding the fundamental mechanisms that assure a constant supply of energy to our tissues and organs, regardless of how the demand might change in response to the environment and over the course of seconds, hours, days, or seasons. It is based on a generator—the Krebs cycle—that burns fat, carbohydrates, and protein with equal facility, and then a supply chain from the adipose tissue that ensures the circulation of fuels at a level that will always be more than adequate for the needs at hand. “The high degree of metabolic activities present in the fat tissues,” as Hilde Bruch explained, “becomes understandable as necessary for a continuous reserve for energy requirements. Instead of a savings account for unneeded surplus, as fat deposits have commonly been described, a coin purse would be a far closer analogy. Fat tissues contain the ready cash for all the expenditures of the organism. Only when the organism does not or cannot draw on the ready cash for its daily business is it put into depots, and excessive replenishment, through overeating, takes place.”

To understand the path of events that leads to obesity, “the big question,” as Bruch noted, was “why the