Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Obesity is a vast and ever-expanding problem in affluent societies, which we have so far failed to confront. Over 20% of Western European and North American adults are overweight to a degree which may potentially shorten their life expectancy. Obesity has well-known associations with non-insulin-dependent diabetes (NIDDM), hypertension, dyslipidaemia and coronary heart disease, as well as less obvious links with diseases such as osteoarthrosis and various malignancies; it also causes considerable problems through reduced mobility and decreased quality of life. The overall financial burden of obesity is impossible to calculate precisely, but may account for 6-8% of total health-care expenditure in North America [1] (similar estimates probably apply to Western Europe). Obesity is difficult to treat and many patients remain obstinately overweight despite our best efforts. The available options range from behavioural therapy to gastrointestinal surgery and include numerous drugs designed to suppress appetite or increase energy expenditure. As in many other areas of medicine, the length and diversity of this list are reliable signs that effective treatment is still beyond our reach. This article argues that new anti-obesity drugs may emerge from recent advances in understanding the control of energy balance in rodents. The discussion is structured around neuropeptide Y (NPY), a major brain peptide which at present appears to be important in regulating energy balance and seems a promising candidate for therapeutic exploitation.