EVIDENCE FOR INVOLVEMENT OF THE MELANOCORTIN MC4 RECEPTOR IN THE EFFECTS OF LEPTIN ON FOOD-INTAKE AND BODY-WEIGHT

The hypothesis that the melanocortin MC4 receptor mediates the homeost atic effects of leptin was tested. Leptin (0.3 nmol, i.c.v.) lowered f ood intake at 4 and 24 h and body weight at 24 h. This effect was inhi bited by pretreatment with an analogue of melanocyte stimulating hormo ne (MSH), the selective melanocortin MC4 receptor antagonist HS014 (cy clic ys(11),D-Nal(14),Cys(18),Asp-NH222]-beta-MSH11-22, 0.3 nmol, i.c. v.). HS014 alone at this dose did not modify food intake or body weigh t. At a higher dose (1.0 nmol, i.c.v.) HS014 stimulated food intake an d this orexigenic effect of HS014 was attenuated by leptin pretreatmen t (0.3 nmol, i.c.v.). These results confirm earlier findings that lept in inhibits food intake and lowers body weight via the melanocortin sy stem and suggest that leptin affects signalling at the melanocortin MC 4 receptor. (C) 1998 Elsevier Science B.V. All rights reserved.