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Publication : Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue.

First Author  Voss-Andreae A Year  2007
Journal  Endocrinology Volume  148
Issue  4 Pages  1550-60
PubMed ID  17194736 Mgi Jnum  J:129583
Mgi Id  MGI:3769818 Doi  10.1210/en.2006-1389
Citation  Voss-Andreae A, et al. (2007) Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Endocrinology 148(4):1550-60
abstractText  The central melanocortin 4 receptor (MC4R) plays a critical role in energy homeostasis, although little is known regarding its role in the regulation of adaptive thermogenesis of brown adipose tissue (BAT). Here we show using retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons in multiple nuclei of the central nervous system known to regulate sympathetic outflow polysynaptically connect with interscapular BAT (IBAT). Furthermore, we show that MC4R-/- and agouti-related peptide-treated mice are defective in HF diet-induced up-regulation of uncoupling protein 1 in IBAT. Additionally, MC4R-/- mice exposed to 4 C for 4 h exhibit a defect in up-regulation of uncoupling protein 1 levels in IBAT. Our results provide a neuroanatomic substrate for MC4R regulating sympathetically mediated IBAT thermogenesis and demonstrate that the MC4R is critically required for acute high-fat- and cold-induced IBAT thermogenesis.
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