Uncoupling proteins: the unravelling of obesity?

Increased understanding of mechanisms may lead, in time, to better drugs

Obesity is becoming a worldwide epidemic, with one in three people in the United States now obese and an increasing prevalence of obesity in developing countries. The discovery of the hormone leptin in 19941 was critical to our understanding of some of the mechanisms of obesity, and an explosion of research into the molecules involved in the normal control of appetite and energy expenditure has resulted. Once these are better defined potential genetic and pharmacological approaches to treating obesity will be opened up. Of particular interest are leptin itself (and how this circulating hormone may regulate appetite via receptors in the hypothalamus) and uncoupling proteins, which are molecules outside the brain that may influence energy expenditure.

Leptin's existence—and the demonstration that leptin deficient mice lose weight if they are given the hormone—represents an intellectual milestone. Obesity should no longer be thought of as a lack of will power: body weight is subject to physiological control. In Cambridge three morbidly obese children have recently been identified as having almost total leptin deficiency.2 One child has been receiving leptin supplements, and the results …