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 rai sed the possibility of effective pharmaceutical control of the energy balan ce. Leptin is secreted from adipocytes in proportion to fat mass in both hu mans and rodents, and circulating leptin is thought to act on the hypothala mus to inhibit feeding and stimulate energy expenditure. Hyperleptinemia ap pears to accompany human obesity, suggesting the development of resistance to leptin's anorexigenic actions, although it was hoped that this resistanc e could be overcome by administration of exogenous leptin. Results from cli nical trials suggest that the response to leptin administration is variable , and while this may be an effective treatment for obesity in some individu als, it is unlikely to be a universal treatment for the disease. Current re search has now turned to examining the factors involved in potentiating lep tin's effects in the brain and the search for leptin analogs or neuropeptid es involved in regulating the leptin pathway is under way in earnest, as th ese may yet prove to be the key to effective treatment for human obesity. ( C) 2000 Wiley-Liss, Inc.