Neuropeptides, the hypothalamus and obesity: insights into the central control of body weight.

Body weight tends to remain relatively stable for long periods over an adult's lifespan. Dieting can reduce weight by 5-10%, but in most individuals attempts to lose larger amounts of weight are counteracted by a reduction in energy expenditure and an increase in hunger. The fact that body weight appears to be actively defended in this manner suggests that it is homeostatically regulated at a certain "set-point". Such a mechanism is likely to be centrally controlled by the brain since the hypothalamus can sense the amount of adipose tissue stored in the body and can alter both energy intake and expenditure. Over the past four years a number of major advances have reinforced the critical role the brain may play in controlling body weight, and these have greatly enhanced our understanding of this area. Advances have included the identification of several genetic mutations that cause obesity in animal models, examination of the metabolic consequences of such mutations and the development of mice with genetically engineered altered neuropeptide levels. This review summarises what has been recently discovered about the regulation of body weight by the brain and how this may be disrupted in obesity.