Malthus said human population was limited by starvation. We are the survivors of previous rounds of starvation. Obesity is a survival characteristic! Unsurprisingly, now food is plentiful we are dying of obesity, and ways of controlling appetite are needed. It is thus essential to understand how the brain controls energy expenditure and appetite. The hypothalamus is the key centre regulating energy balance. It integrates several inputs. Higher centres give psychological information (food palatability, environmental dangers during feeding etc). There is also more basic information (sleep/wake cycles, pain etc). Somatic afferent input is processed and relayed through the brain stem, particularly the dorsal vagal complex. Circulating gut hormones which influence feeding, including ghrelin, cholecystokinin and Peptide YY, act on the vagus in the periphery, the brain stem via the area postrema, and directly on the hypothalamic arcuate nucleus. Larger circulating hormones are transported across the blood brain barrier by specific transport mechanisms. These inputs and other hypothalamic circuits converge on the arcuate nucleus, where two important neurone types are present: an appetite stimulatory, energy expenditure inhibitory group producing Agouti-related protein and Neuropeptide Y, and an appetite inhibitory, energy expenditure enhancing group producing Cocaine and Amphetamine Regulated Transcript and Pro-opiomelanocortin (alpha-melanocyte-stimulating hormone). These two neurone types both project to the paraventricular nucleus. Melanocyte-Stimulating Hormone is the agonist at the appetite inhibitory Melanocortin (4) receptor and Agouti-related protein is a powerful controlling antagonist at this same receptor. Cocaine and Amphetamine Regulated Transcript has an inhibitory receptor and Neuropeptide Y stimulates appetite through the Y1 and Y5 receptors. The paraventricular nucleus actuates 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 paraventricular nucleus delivers co-ordinated changes in energy balance.
24 - 26 Mar 2003
British Endocrine Societies