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APPETITE, OBESITY, AND DIGESTION

Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence

¹Department of Biology and Center for Behavioral Neuroscience, Georgia State University, Atlanta; ²Department of Foods and Nutrition, University of Georgia, Athens, Georgia; and ³Centre de Recherche de l'Hôpital Laval, Sainte-Foy, Québec, Canada

Submitted 9 March 2008 ; accepted in final form 10 June 2008

A precise understanding of neural circuits controlling lipid mobilization and thermogenesis remains to be determined. We have been studying the sympathetic nervous system (SNS) contributions to white adipose tissue (WAT) lipolysis largely in Siberian hamsters. Central melanocortins are implicated in the control of the sympathetic outflow to WAT, and, moreover, the melanocortin 4 receptors (MC4-R) appear to be principally involved. We previously found that acute third ventricular melanotan II (MTII; an MC3/4-R agonist) injections increase sympathetic drive (norepinephrine turnover) to interscapular brown adipose tissue (IBAT) and IBAT temperature. Here we tested whether MC4-R mRNA is expressed in IBAT SNS outflow neurons using in situ hybridization for the former and injections of the transneuronal viral retrograde tract tracer, pseudorabies virus (PRV) into IBAT, for the latter. Significant numbers of double-labeled cells for PRV and MC4-R mRNA were found across the neuroaxis (mean of all brain sites 60%), including the hypothalamic paraventricular nucleus (PVH; 80%). Acute parenchymal MTII microinjections into the PVH of awake, freely-moving hamsters, using doses below those able to increase IBAT temperature when injected into the third ventricle, increased IBAT temperature for as long as 4 h, as measured by temperature transponders implanted below the tissue. Collectively, these data add significant support to the view that central melanocortins are important in controlling IBAT thermogenesis via the SNS innervation of this tissue, likely through the MC4-Rs.

Siberian hamsters; in situ hybridization; pseudorabies virus; tract tracing; melanocortins

This article has been cited by other articles:

				C. K. Song, G. J. Schwartz, and T. J. Bartness Anterograde transneuronal viral tract tracing reveals central sensory circuits from white adipose tissue Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R501 - R511. [Abstract] [Full Text] [PDF]