Endocrine Abstracts

The key centre regulating energy balance is the hypothalamus. It receives several inputs. First there is the input from the CNS. Higher centres (psychological input) give information about food palatability, likely environmental dangers during feeding etc. There is also information of a more basic kind (sleep/wake cycles, pain, metabolic disturbance etc). Secondly there is somatic afferent input, for example from the vagus, which is mainly processed and relayed through the brain stem, particularly the dorsal vagal complex. Circulating gut hormones, ghrelin to stimulate and CCK, GLP1, oxyntomodulin and PYY to inhibit, have been shown to act both on the vagus in the periphery, in the brain stem via the defective blood brain barrier in the area postrema and directly on the hypothalamic arcuate nucleus. Larger circulating hormones, such as leptin and insulin, have specific transport mechanisms which 'pump' them across the blood brain barrier. All of these inputs, and other hypothalamic circuits impinging on energy balance, converge on the arcuate nucleus. Here two neurone types are recognised. First there is an appetite inhibitory, energy expenditure enhancing group producing CART and POMC (alpha MSH). Second there is an appetite stimulatory, energy expenditure inhibitory group producing Agrp and NPY. These two neurone types both project to the PVN. MSH is the agonist on the appetite inhibitory MC4 receptor and Agrp is a powerful controlling antagonist at this same receptor. CART has its own inhibitory receptor and NPY probably stimulates appetite through both the Y1 and Y5 receptors. The PVN in turn activates changes in appetite and energy expenditure through pathways outside the hypothalamus as yet undetermined. This picture now forms the core dogma - the arcuate nucleus senses and integrates and the PVN delivers co-ordinated changes in energy balance.