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Central Melanocortin Receptors Mediate Changes in Food Intake in the Rhesus Macaque¹

Divisions of Reproductive Biology (F.H.K., A.S., J.L.C.) and Neuroscience (F.H.K., K.L.G., A.S., M.S.S., J.L.C.), Oregon Regional Primate Research Center, and Department of Physiology and Pharmacology, Oregon Health Sciences University (M.S.S., J.L.C.), Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Frank Koegler, Ph.D., Oregon Regional Primate Research Center, 505 NW 185th Avenue, Beaverton, Oregon 97006. E-mail: koeglerf{at}ohsu.edu

In rodents, stimulation of melanocortin-3 and -4 receptor subtypes (MC3-R and MC4-R) causes a reduction in food intake, whereas antagonism of MC3-R and MC4-R increases food intake. This report describes the effects of the stable MSH analog, NDP-MSH ([Nle⁴, D-Phe⁷]MSH), and the endogenous MSH receptor antagonist, agouti-related protein, on feeding behavior in adult male rhesus macaques. Infusion of NDP-MSH into the lateral cerebral ventricle dose dependently suppressed intake of a normally scheduled meal without affecting nonfeeding behaviors. Conversely, infusion of agouti-related protein stimulated food intake during the scheduled afternoon meal. In addition to these physiological experiments, the effect of fasting on hypothalamic POMC gene expression was assessed by in situ hybridization. Missing a single meal or fasting for 48 h caused a similar reduction in POMC gene expression in the arcuate nucleus. These results demonstrate that in the primate, central melanocortin receptors can acutely regulate food intake and suggest that the central melanocortinergic system is a physiological regulator of energy balance in primate species.

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