MELANIN-CONCENTRATING HORMONE IS A POTENT ANORECTIC PEPTIDE REGULATEDBY FOOD-DEPRIVATION AND GLUCOPENIA IN THE RAT

Melanin-concentrating hormone is a cyclic nonadecapeptide that is prod uced almost exclusively in neurons of the lateral hypothalamus and sub zona incerta areas while fibers are widespread in the rat brain. Such a localization strongly suggests that this peptide might participate as neurotransmitter/neuromodulator in the control of feeding behavior. In this study we examined first the influence of rat melanin-concentr ating hormone on feeding behavior at different times either in the lig ht or in the dark period (light off at 18.00 h) of the day in fed Wist ar rats. Intracerebroventricular injection of rat melanin-concentratin g hormone (1-100 ng per rat) at 18.00 h reduced food consumption as ea rly as 2 h after injection and for the next 24 h. In addition, similar anorectic effect was noted after bilateral administration of 1 ng mel anin-concentrating hormone into the lateral hypothalamic area at 11.30 h but not at 16.30 h, These findings strongly suggest that rat melani n-concentrating hormone may exert inhibitory control over food intake behavior depending on the circadian rhythm. Second, we investigated th e modifications induced by food deprivation/refeeding on melanin-conce ntrating hormone messenger RNA levels in Wistar rats. Total RNA was is olated from whole hypothalamic dissections and the contents of melanin -concentrating hormone messenger RNA, beta-actin messenger RNA (taken as sample control) and neuropeptide Y messenger RNA (taken as control of food-deprivation paradigms) were assessed by using northern blottin g. The time-course of messenger RNA expression was determined in group s of rats deprived for 24, 48 and 72 h and revealed a three-fold induc tion of melanin-concentrating hormone messenger RNA by 24 and 48 h, wi th reduced increase at 72 h. As expected, the same treatment led to a three-fold increase in neuropeptide Y messenger RNA content by 48 and 72 h. Refeeding groups of animals for up to 72 h after 24 h of food de privation resulted in full restoration of melanin-concentrating hormon e messenger RNA levels by 24 h. Strikingly, a large range of variation s in melanin-concentrating hormone messenger RNA content between indiv iduals was observed in food-deprived versus controls or refed rats sug gesting that genetic or environmental factors may alter response in me lanin-concentrating hormone gene activity after food deprivation. Fina lly, we investigated the effects of short-term glucoprivation induced by intraperitoneal administration of either 2-deoxy-D-glucose or insul in on melanin-concentrating hormone messenger RNA expression. A transi tory increase in melanin-concentrating hormone messenger RNA content w as noted Ih after 2-deoxy-D-glucose injection while melanin-concentrat ing hormone messenger RNA levels rose two-fold only 5 h after insulin treatment. These results indicate that 2-deoxy-D-glucose and insulin a ctivate melanin-concentrating hormone gene expression through likely d istinct regulatory pathways.