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Hypothalamic Melanin-Concentrating Hormone Is Induced by Cold Exposure and Participates in the Control of Energy Expenditure in Rats

Departments of Internal Medicine (M.P., M.A.T., H.V.N., C.T.S., A.L.G., J.B.C., M.J.A.S., L.A.V.) and Physiology and Biophysics (V.A., G.V., M.C.C.G.M., A.C.B., E.M.C.), State University of Campinas; and Department of Zoology (A.P.C.-N.), Paulista State University, Campus Rio Claro–State University of Sao Paulo, 13083-970 Campinas SP, Brazil

Address all correspondence and requests for reprints to: Lício A. Velloso, Departamento de Clínica Médica, FCM-UNICAMP, 13083-970 Campinas SP, Brazil. E-mail: lavelloso{at}fcm.unicamp.br.

Short-term cold exposure of homeothermic animals leads to higher thermogenesis and food consumption accompanied by weight loss. An analysis of cDNA-macroarray was employed to identify candidate mRNA species that encode proteins involved in thermogenic adaptation to cold. A cDNA-macroarray analysis, confirmed by RT-PCR, immunoblot, and RIA, revealed that the hypothalamic expression of melanin-concentrating hormone (MCH) is enhanced by exposure of rats to cold environment. The blockade of hypothalamic MCH expression by antisense MCH oligonucleotide in cold-exposed rats promoted no changes in feeding behavior and body temperature. However, MCH blockade led to a significant drop in body weight, which was accompanied by decreased liver glycogen, increased relative body fat, increased absolute and relative interscapular brown adipose tissue mass, increased uncoupling protein 1 expression in brown adipose tissue, and increased consumption of lean body mass. Thus, increased hypothalamic MCH expression in rats exposed to cold may participate in the process that allows for efficient use of energy for heat production during thermogenic adaptation to cold.

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