The search for new ways to treat obesity

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Abstract
Obesity must be ranked among the most intractable of our health problems. In 1999, the Centers for Disease Control and Prevention reported (1) that obesity, defined as a body mass index ≧30,† had risen in the adult United States population from 12.0% in 1991 to 17.9% in 1998. At this time we have little evidence for abatement of the “epidemic,” although warnings from health officials and physicians are numerous and most individuals consider obesity both unsightly and hazardous. Treatments with many different diets, behavior modification, nutrition counseling, over-the-counter drugs, and dietary supplements are the basis for a lucrative industry that has hardly made a dent in the problem. This issue of PNAS includes a report (2) on an agent affecting fatty acid synthesis that may or may not enter the battle against obesity but is sure to cast some light on the nature of the problem. How can we understand the intractability of this national nuisance? The unwanted weight of the obese is that of triglyceride stored in adipose tissue. Storage of this calorically dense substance is held to account by the simple thermodynamic expression, Δ E = Q − W. One cannot increase energy storage (E) without an inequality between what you eat (Q) and what you burn (W). But there is some surprising arithmetic in the account ledger of calories. Consider the all-too-common case of Mr. X who joined the ranks of the obese by gradually accumulating 75,000 kcal (1 kcal = 4.18 kJ) in his adipose depot over the first 5 years of happy marriage. The extra 75,000 kcal is just a ripple in the vast stream of 4 million or 5 million calories that flux in and out of Mr. X's body over 5 years. In fact, his excess intake averages only 40 …