Gut hormones: a weight off your mind.

The increasing prevalence of obesity and the associated morbidity and mortality has resulted in a major research effort to identify mechanisms that regulate appetite. It is well established that the hypothalamus and brain stem are major sites in the central nervous system (CNS) that regulate appetite. Until recently the missing element has been how information regarding food intake and energy stores is communicated to the CNS. Gut hormones have recently been found to be an important element in this regulation, communicating information regarding food intake to the CNS. Several gut hormones have been found to exert anorectic effects. These include members of the Pancreatic Polypeptide (PP)-fold family, namely PP itself and also peptide tyrosine-tyrosine (PYY), the first gut hormone shown to have appetite-inhibiting properties. The other main class of anorectic gut hormones are those derived by proteolytic processing from proglucagon, most importantly glucagon-like peptide-1 (GLP-1) and oxyntomodulin. All of these are currently being investigated as the basis of treatments to prevent the development of obesity. So far the only gastrointestinal hormone demonstrated to stimulate appetite is ghrelin. Potential sites and mechanisms of action and therapeutic use of these gastrointestinal hormones are discussed.