Hypothalamic control of energy balance

Over the last decade, understanding of the circuits and molecules involved in the regulation of energy balance has expanded dramatically. A complex system has evolved which allows the brain to read, interpret and integrate a wide range of signals and to elicit appropriate changes in food intake and energy expenditure as a result of the information. A series of short-term signals derived from the gastrointestinal tract, such as cholecystokinin, govern meal size. Other hormones e.g. insulin and leptin, and circulating nutrients offer long-term regulation. These signals act at a variety of central nervous system sites, but the majority of pathways converge on the hypothalamus, which itself contains numerous peptides and neurotransmitters that influence feeding and energy expenditure. Mutations in key components of these circuits underlie some of the syndromes of genetic obesity in rodents, but are responsible for only a small percentage of human obesity--which is largely attributed to an adverse lifestyle. However, various abnormalities have been identified in dietary-obese rodents, which is the closest model to 'common' human obesity. The relevance of these to energy homeostasis in humans remains uncertain, but some are likely to emerge as therapeutic targets for the treatment of both obesity and eating disorders.