The future of obesity treatment.
Obesity is rapidly becoming a worldwide epidemic, with significant consequences in terms of clinical burden and economic costs in treating its complications, so effective new approaches are urgently needed. Development of new drugs in this therapeutic area requires a detailed understanding of the physiology underlying body weight regulation. Recently several significant advances have been made in this area, including the identification of the appetite regulating hormone, leptin, and a detailed understanding of its targets in the central nervous system (CNS), such as neuropeptide Y (NPY) and the melanocortin-4 receptor. The observation that some humans with severe childhood-onset obesity have defects in these regulatory systems has confirmed their relevance in humans as well as in animal models, and the search is now on to produce drugs which act on these and other CNS targets such as glucagon-like peptide I and the orexins to help reduce body weight. Other recently identified targets outside the central nervous system include agents acting to inhibit digestive enzymes, specifically pancreatic lipase in the form of orlistat (which has recently been licensed for obesity treatment), and looking to the future, the possibility of altering energy expenditure by modulating the newly identified uncoupling proteins is being considered. It should be remembered however, that pharmacotherapy for obesity is unlikely to provide a 'magic bullet', and that diet and lifestyle changes are likely to remain the cornerstone of treatment for the foreseeable future.
Wilding
J
J
University Hospital Aintree, Liverpool, UK.
D000328:Adult; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002648:Child; D015195:Drug Design; D004734:Energy Metabolism; D005246:Feedback; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology