Good Calories, Bad Calories

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 cells 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 finally 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 “small component” of the fuel we use during fasting, and this drops away to “none at all” if our fast continues for more than a week. In such cases, fat will supply 85 percent of our energy needs, and protein the rest, after its conversion to glucose in the liver. Still, because the brain and central nervous system typically burn 120 to 130 grams of glucose a day, nutritionists insisted (as many still 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 Rockefeller University, Robert Gordon at NIH, and Sigfrid Laurell of the University of Lund in Sweden that reported the development of a technique for measuring the concentration of fatty acids in the circulation. All 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 follow, 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 cells 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 falls 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 naturally 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.