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Obesity: a failure of homeostasis because of hedonic rewards: response to the letter from Gary Taubes

In his nearly 5000-word response to my book review (1), Mr Taubes has raised a number of issues. Before responding to specific issues, I wanted to contrast his ‘model’ of how obesity develops with mine. This may answer many of the questions that readers have about his book (2) and my review of it (3). When I was in clinical training, my mentors (Fuller Albright, Rosalind Pitt-Rivers and Edwin B. Astwood) encouraged me to use diagrams and models to explain my findings and outline future experiments. I have tried to follow their advice in this letter. In my review (3) of Good Calories, Bad Calories, it did not seem appropriate to insert my own concept of obesity into the review but rather to point out the strengths and weaknesses of the book as I interpreted them. In his response to my book review, Mr Taubes has opened the door for me to contrast his hypothesis for obesity with mine. The hypothesis for obesity and its treatment developed in Good Calories Bad Calories (2) is repeated in much more succinct form in his letter (1). My interpretation is shown below. It is based on two sentences from the letter, which say ‘excess accumulation [of fat] is caused fundamentally by the effect of dietary carbohydrate on insulin and of insulin on adipocytes’ and several pages later – ‘one reason why the Atkins diet is scientifically compelling in this context is that it is a very high-fat diet, and yet leads to weight loss, at least in the short term, not weight gain’. Supporting these statements is a later one reading ‘. . . the disorder [obesity] is fundamentally caused by the effect of carbohydrates on insulin and insulin on fat accumulation . . .’. I have sketched my interpretation of this model in Fig. 1 along with the low-carbohydrate treatment that he proposes. In his book and letter, Mr Taubes says that the cause of obesity was established before World War II when European research concluded that gluttony and inactivity were not the cause but rather a metabolic hormonal drive to accumulate excess fat. A little later, the letter says that the regulation of fat accumulation was established in 1965 and ‘has never been controversial’ (2). ‘Insulin is the principal regulator of fat metabolism’. However, in 1965, leptin was unknown. Its discovery in 1994 (4) produced the type of paradigm shift that Kuhn describes in his book The Structure of Scientific Revolutions (5). The absence of leptin produces massive obesity that is dependent on glucocorticoids (6). For me the discovery of leptin and its dependence on glucocorticoids made an ‘insulin-centric’ view of obesity incomplete. My homeostatic model, shown in Fig. 2 on the left, was developed from studies with genetically inherited obesity in rats, which we now know is due to a defect in the leptin receptor. As a control I used obesity produced by damaging specific areas of the brain (6). Obesity because of brain lesions is prevented or reversed by adrenalectomy, which removes glucocorticoids. These findings led me and my colleagues to propose an endocrine and metabolic hypothesis for the development of obesity in 1979 (6). The discovery of leptin added another dimension to this model. The homeostatic model shown below starts with the First Law of Thermodynamics, which states that the change of energy in a closed system is the difference between the heat added to the system and the work done by the system. In an equation it looks like this: