Good Calories, Bad Calories (70 page)

Among their discoveries is that both dietary fat and a considerable portion of the carbohydrates we consume are stored as fat—or, technical y, triglycerides—in the adipose tissue before being used for fuel by the cel s. 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 cel s 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 final y 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 control ing 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 control ed, Wertheimer wrote, by “a factor acting directly on the cel ,” 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 cel s 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 cel s, which are those compartments commonly referred to as the “power plants” of the cel s. 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 wil 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. “Al 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 wil 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 al 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 metabolism is shifted in the direction of storage away from oxidation?” Why is fat deposited in the adipose tissue to accumulate in excess of its mobilization for fuel use? Once again, this has little to do with calories consumed or expended, but addresses the questions of how the cel s utilize these calories and how the body regulates its balance between fat deposition and mobilization, between lipogenesis (the creation of fat) and lipolysis (the breakdown of triglycerides into fatty acids, their escape from the fat tissue, and their subsequent use as fuel). “Since it is now assumed that the genes and enzymes are closely associated,” Bruch wrote in 1957, “it is conceivable that people with the propensity for fat accumulation have been born with enzymes that are apt to facilitate the conversion of certain reactions in that direction.”

The third phase of this research final y established the dominant role of fatty acids in supplying energy for the body, and the fundamental role of insulin and adipose tissue as the regulators of energy supply. As early as 1907, the German physiologist Adolf Magnus-Levy had noted that during periods of fasting between meals “the fat streams from the depots back again into the blood…as if it were necessary for the immediate needs of the combustion processes of the body.” A decade later, Francis Benedict reported that blood sugar provides only a “smal component” of the fuel we use during fasting, and this drops away to “none at al ” if our fast continues for more than a week. In such cases, fat wil supply 85 percent of our energy needs, and protein the rest, after its conversion to glucose in the liver. Stil , because the brain and central nervous system typical y burn 120 to 130 grams of glucose a day, nutritionists insisted (as many stil do) that carbohydrates must be our primary fuel, and they remained skeptical of the notion that fat plays any role in energy balance other than as a long-term reserve for emergencies.

Among physiologists and biochemists, any such skepticism began to evaporate after Wertheimer’s review of fat metabolism appeared in 1948. It vanished after the 1956 publication of papers by Vincent Dole at Rockefel er University, Robert Gordon at NIH, and Sigfrid Laurel of the University of Lund in Sweden that reported the development of a technique for measuring the concentration of fatty acids in the circulation. Al three articles suggested that these fatty acids were the form in which fat is burned for fuel in the body. The concentration of fatty acids in the circulation, they reported, is surprisingly low immediately after a meal, when blood-sugar levels are highest, but then increases steadily in the hours that fol ow, as the blood sugar ebbs. Injecting either glucose or insulin into the circulation diminishes the level of fatty acids almost immediately. It’s as though our cel s have the option of using fatty acids or glucose for fuel, but when surplus glucose is available, as signaled by rising insulin or blood-sugar levels, the fatty acids are swept into the fat tissue for later use. The concentration of circulating fatty acids rises and fal s in “relation to the need” for fuel, wrote Gordon. And because injections of adrenaline cause a flooding of the circulation with fatty acids, and because adrenaline is natural y released by the adrenal glands as an integral part of the flight-fight response, Gordon suggested that the concentration of fatty acids also rises in relation to “the anticipated need” for fuel.

In 1965, the American Physiological Society published an eight-hundred-page Handbook of Physiology dedicated to the latest research on adipose-tissue metabolism. As this volume documented, several fundamental facts about the relationship between fat and carbohydrate metabolism had become clear. First, the body wil burn carbohydrates for fuel, as long as blood sugar is elevated and the reserve supply of carbohydrates stored as glycogen in the liver and muscles is not being depleted. As these carbohydrate reserves begin to be tapped, however, or if there’s a sudden demand for more energy, then the flow of fatty acids from the fat tissue into the circulation accelerates to take up the slack. Meanwhile, a significant portion of the carbohydrates we consume and al of the fat wil be stored as fat in our fat cel s before being used for fuel. It’s this stored fat, in the form of fatty acids, that wil then provide from 50 to 70 percent of al the energy we expend over the course of a day. “Adipose tissue is no longer considered a static tissue,” wrote the Swiss physiologist Albert Renold, who coedited the Handbook of Physiology; “it is recognized as what it is: the major site of active regulation of energy storage and mobilization, one of the primary control mechanisms responsible for the survival of any given organism.”

Since the excessive accumulation of fat in the fat tissue is the problem in obesity, we need to understand this primary control mechanism. This means, first of al , that we have to appreciate the difference between triglycerides and free fatty acids. They’re both forms fat takes in the human body, but they play very different roles, and these are tied directly to the way the oxidation and storage of fats and carbohydrates are regulated.

When we talk about the fat stored in the adipose tissue or the fats in our food, we’re talking about triglycerides. Oleic acid, the monounsaturated fat of olive oil, is a fatty acid, but it is present in oils and meats in the form of a triglyceride. Each triglyceride molecule is composed of three fatty acids (the “tri”), linked together on a backbone of glycerol (the “glyceride”). Some of the triglycerides in our fat tissue come from fat in our diet. The rest come from carbohydrates, from a process known as de novo lipogenesis, which is Latin for “the new creation of fat,” a process that takes place both in the liver and, to a lesser extent, in the fat tissue itself. The more carbohydrates flooding the circulation after a meal, the more wil be converted to triglycerides and stored as fat for future use (perhaps 30 percent of the carbohydrates in any one meal). “This lipogenesis is regulated by the state of nutrition,” explained Wertheimer in an introductory chapter to the Handbook of Physiology: “it is decreased to a minimum in carbohydrate deficiency and accelerated considerably during carbohydrate availability.”*114

A second critical point is that while the fat is stored as triglycerides it enters and exits the fat cel s in the form of fatty acids—actual y, free fatty acids, to distinguish them from the fatty acids bound up in triglycerides—and it’s these fatty acids that are burned as fuel in the cel s. As triglycerides, the fat is locked into the fat cel s, because triglycerides are too big to slip through the cel membranes. They have to be broken down into fatty acids—the process technical y known as lipolysis—before the fat can escape into the circulation. The triglycerides in the bloodstream must also be broken down into fatty acids before the fat can diffuse into the fat cel s. It’s only reconstituted into triglycerides, a process cal ed esterification, once the fatty acids have passed through the wal s of the blood vessels and the fat-cel membranes and are safely inside. This is true for al triglycerides, whether they originated as fat in the diet or were converted from carbohydrates in the liver.

Inside the fat cel s, triglycerides are continuously broken down into their component fatty acids and glycerol (i.e., in lipolysis), and fatty acids and glycerol are continuously reassembled into triglycerides (i.e., esterified)—a process known as the triglyceride/fatty-acid cycle. Any fatty acids that are not immediately repackaged back into triglycerides wil slip out of the fat cel and back into the circulation—“a ceaseless stream of [free fatty acids], a readily transportable source of energy, into the bloodstream,” as it was described in the Handbook of Physiology by one team of NIH researchers.

Some of these free fatty acids wil be taken up by the tissues and organs and used as fuel. Perhaps as much as half of them wil not. These wil be incorporated in the liver back into triglycerides, loaded on lipoproteins,*115 and shipped back again to the fat tissue. And so fatty acids are continuously slipping from the fat tissue into the circulation, while those fatty acids that aren’t immediately taken up and used for fuel are continuously being reconverted to triglycerides and transported back to the fat tissue for storage. “The storage of triglyceride fat in widely scattered adipose tissue sites is a remarkably dynamic process,” explained the University of Wisconsin endocrinologist Edgar Gordon in 1969, “with the stream of fatty acid carbon atoms flowing in widely fluctuating amounts, first in one direction and then the other in a finely adjusted minute by minute response to the fuel requirements of energy metabolism of the whole organism.”

This remarkably dynamic process, however, is regulated by a remarkably simple system. The flow of fatty acids out of the fat cel s and into the circulation depends on the level of blood sugar available. The burning of this blood sugar by the cel s—the oxidation of glucose—depends on the availability of fatty acids to be burned as fuel instead.

A single molecule plays the pivotal role in the system. It goes by a number of names, the simplest being glycerol phosphate. This glycerol-phosphate molecule is produced from glucose when it is used for fuel in the fat cel s and the liver, and it, too, can be burned as fuel in the cel s. But glycerol phosphate is also an essential component of the process that binds three fatty acids into a triglyceride. It provides the glycerol molecule that links the fatty acids together.†116 In other words, a product of carbohydrate metabolism—i.e., burning glucose for fuel—is an essential component in the regulation of fat metabolism: storing fat in the fat tissue. In fact, the rate at which fatty acids are assembled into triglycerides, and so the rate at which fat accumulates in the fat tissue, depend primarily on the availability of glycerol phosphate. The more glucose that is transported into the fat cel s and used to generate energy, the more glycerol phosphate wil be produced. And the more glycerol phosphate produced, the more fatty acids wil be assembled into triglycerides. Thus, anything that works to transport more glucose into the fat cel s—insulin, for example, or rising blood sugar—wil lead to the conversion of more fatty acids into triglycerides, and the storage of more calories as fat.