It has previously been established that the hypothalamic arcuate nucleus receives appetite input signals from both the brain stem and the peripheral circulation. Two neuronal types control food intake, an inhibitory neurone secreting alpha MSH and CART and a stimulatory neurone secreting NPY and AGRP. It was established that leptin activated the inhibitory neurone and inhibited the appetite stimulating neurone. The intestinal hormone, PYY, released after food ingestion acted in a similar way. In contrast the 'hormone of hunger' ghrelin, released from the stomach in the fasting state, stimulated the appetite stimulating neurones and inhibits the appetite inhibitory neurones i.e. acts in an opposite direction. We have now identified two further gut hormones that influence appetite, oxyntomodulin and pancreatic polypeptide. Oxyntomodulin is released after food in a similar way to PYY and has a similar action on appetite. It is in the same family of peptides as GLP-1, which was previously shown to have an affect on appetite. GLP-1, however, also releases insulin (thereby causing hypoglycaemia) and has an affect on both gastric emptying rate and glucagon release. PP is in the same family as NPY and PYY and is released from the PP cells in the islets of Langerhans, again after food ingestion and in parallel to insulin. Together these gut hormones form an integrated appetite regulatory system which tells the brain when the gut is empty and when it is full and regulates meal size. Of considerable interest is the finding that in obesity the release of these hormones is altered and at least some of the change tends to perpetuate the condition and are thus clinically helpful. Therapeutic possibilities will be discussed.
22 - 24 Mar 2004
British Endocrine Societies