MAHOGANY (MG) STIMULATES FEEDING AND INCREASES BASAL METABOLIC-RATE INDEPENDENT OF ITS SUPPRESSION OF AGOUTI

The mahogany (mg) locus originally was identified as a recessive suppr essor of agouti, a locus encoding a skin peptide that modifies coat co lor by antagonizing the melanocyte-stimulating hormone receptor or MC1 -R. Certain dominant alleles of agouti cause an obesity syndrome when ectopic expression of the peptide aberrantly antagonizes the MC4-R, a related melanocyte-stimulating hormone receptor expressed in hypothala mic circuitry and involved in the regulation of feeding behavior and m etabolism. Recent work has demonstrated that mg, when homozygous, bloc ks not only the ability of agouti to induce a yellow coat color when e xpressed in the skin of the lethal yellow mouse (A(Y)), but also the o besity resulting from ectopic expression of agouti in the brain. Detai led analysis of mg/mg A(Y)/a animals, presented here, demonstrates tha t mg/mg blocks the obesity, hyperinsulinemia, and increased linear gro wth induced by ectopic expression of the agouti peptide. Remarkably, h owever, mg/mg did not reduce hyperphagia in the A(Y)/a mouse. Furtherm ore, mg/mg induced hyperphagia and an increase in basal metabolic rate in the C57BL/6J mouse in the absence of A(Y). Consequently, although mahogany is broadly required for agouti peptide action, it also appear s to be involved in the control of metabolic rate and feeding behavior independent of its suppression of agouti.