An anorexic lipid mediator regulated by feeding

Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide. Like anandamide, OEA is produced in cells in a stimulus-depend ent manner and is rapidly eliminated by enzymatic hydrolysis, suggesting a function in cellular signalling(1). However, OEA does not activate cannabin oid receptors and its biological functions are still unknown(2). Here we sh ow that, in rats, food deprivation markedly reduces OEA biosynthesis in the small intestine. Administration of OEA causes a potent and persistent decr ease in food intake and gain in body mass. This anorexic effect is behaviou rally selective and is associated with the discrete activation of brain reg ions (the paraventricular hypothalamic nucleus and the nucleus of the solit ary tract) involved in the control of satiety. OEA does not affect food int ake when injected into the brain ventricles, and its anorexic actions are p revented when peripheral sensory fibres are removed by treatment with capsa icin. These results indicate that OEA is a lipid mediator involved in the p eripheral regulation of feeding.