TY - JOUR
T1 - Mahogany (mg) stimulates feeding and increases basal metabolic rate independent of its suppression of agouti
AU - Dinulescu, Daniela M.
AU - Fan, Wei
AU - Boston, Bruce A.
AU - Mccall, Kathleen
AU - Lamoreux, M. Lynn
AU - Moore, Karen J.
AU - Montagno, Jill
AU - Cone, Roger D.
PY - 1998/10/13
Y1 - 1998/10/13
N2 - The mahogany (mg) locus originally was identified as a recessive suppressor of agouti, a locus encoding a skin peptide that modifies coat color 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 hypothalamic: circuitry and involved in the regulation of feeding behavior and metabolism. Recent work has demonstrated that rag, when homozygous, blocks not only the ability of agouti to induce a yellow coat color when expressed in the skin of the lethal yellow mouse (A(Y)), but also the obesity resulting from ectopic expression of agouti in the brain. Detailed analysis of mg/mg A(Y)/a animals, presented here, demonstrates that mg/mg blocks the obesity, hyperinsulinemia, and increased linear growth induced by ectopic expression of the agouti peptide. Remarkably, however, mg/mg did not reduce hyperphagia in the Aria mouse. Furthermore, 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 appears to be involved in the control of metabolic rate and feeding behavior independent of its suppression of agouti.
AB - The mahogany (mg) locus originally was identified as a recessive suppressor of agouti, a locus encoding a skin peptide that modifies coat color 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 hypothalamic: circuitry and involved in the regulation of feeding behavior and metabolism. Recent work has demonstrated that rag, when homozygous, blocks not only the ability of agouti to induce a yellow coat color when expressed in the skin of the lethal yellow mouse (A(Y)), but also the obesity resulting from ectopic expression of agouti in the brain. Detailed analysis of mg/mg A(Y)/a animals, presented here, demonstrates that mg/mg blocks the obesity, hyperinsulinemia, and increased linear growth induced by ectopic expression of the agouti peptide. Remarkably, however, mg/mg did not reduce hyperphagia in the Aria mouse. Furthermore, 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 appears to be involved in the control of metabolic rate and feeding behavior independent of its suppression of agouti.
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U2 - 10.1073/pnas.95.21.12707
DO - 10.1073/pnas.95.21.12707
M3 - Article
C2 - 9770550
AN - SCOPUS:0032514614
SN - 0027-8424
VL - 95
SP - 12707
EP - 12712
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -