In 1936, when Eugene Du Bois published the third edition of his metabolism textbook, Basal Metabolism in Health and Disease, he described the system that accomplished the regulation of a stable body weight as it was then understood. How much we want to eat on any given day, Du Bois explained, is determined by how much we’ve depleted whatever our body considers the necessary reserves of protein, fat, and carbohydrates. If we then consume more calories than we need, the excess will either be burned off as heat or induce physical activity: “When well nourished, the individual tends to become more energetic and it is quite possible that he will soon burn up his stored fat by extra work or exercise which would not have been undertaken had it not been for the overfeeding.” If we consume less food than we might require to replenish our reserves, then the amount of heat generated in response to a meal is minimized, and the stores of carbohydrates (glycogen), fat, and protein are used to make up the difference. Should the caloric deficit continue, the result is “a gradual lowering of metabolism and a tendency toward restriction of activities, due to a lack of energy and initiative.”

However this homeostatic system works to balance energy intake and output and thus maintain a steady supply of fuel to the cells and a stable body weight, it is extraordinarily complex and involves the entire body. Rony discussed this: “The appetite mechanism, which is but a part, although the most important one, of body weight regulation is in itself a highly complex mechanism involving [the central nervous system], endocrine glands, the gastric neuro-muscular apparatus, and the organs of the glycogen, protein, and fat reserves.” This notion was supported by a host of experimental and clinical studies, as we’ll discuss in Chapter 21, which demonstrated that disturbances in body-weight regulation—like obesity—could be caused by “pathological changes in certain parts of the nervous system, endocrine system and depot organs.”