Leptin and the treatment of obesity

The cloning of the ob gene and subsequent discovery of the weight-reducing protein leptin has revitalized research into body weight regulation and raised the possibility of effective pharmaceutical control of the energy balance. Leptin is secreted from adipocytes in proportion to fat mass in both humans and rodents, and circulating leptin is thought to act on the hypothalamus to inhibit feeding and stimulate energy expenditure. Hyperleptinemia appears to accompany human obesity, suggesting the development of resistance to leptin's anorexigenic actions, although it was hoped that this resistance could be overcome by administration of exogenous leptin. Results from clinical trials suggest that the response to leptin administration is variable, and while this may be an effective treatment for obesity in some individuals, it is unlikely to be a universal treatment for the disease. Current research has now turned to examining the factors involved in potentiating leptin's effects in the brain and the search for leptin analogs or neuropeptides involved in regulating the leptin pathway is under way in earnest, as these may yet prove to be the key to effective treatment for human obesity.