So far, the evidence that supports this hypothesis is quite promising. Leptin levels in the blood do indeed increase with weight gain and decrease with weight loss. Injections of leptin in obese mutant mice cause them to reduce food intake and lose weight (and these injections work even if tiny doses are delivered directly to the hypothalamus). Injections of leptin in db mutant mice have no effect, because there are no leptin receptors in the hypothalamus for the exogenous leptin to activate.
Of those people who are morbidly obese, less than 1 percent harbor DNA mutations that disrupt the function of the leptin gene—a low rate of incidence that is not surprising, as leptin-deficient humans and mice are both in fertile, so these mutations do not pass readily to subsequent generations.
Reprinted by arrangement with Viking, a member of Penguin Group (USA) Inc., from Compass of Pleasure by David Linden. Copyright © 2011 by David J. Linden.