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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 295; no. 2; pp. R417 - R428
• Main Authors: Song, C. Kay, Vaughan, Cheryl H, Keen-Rhinehart, Erin, Harris, Ruth B. S, Richard, Denis, Bartness, Timothy J
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2008
• Subjects: Adipose Tissue, Brown - innervation; alpha-MSH - administration & dosage; alpha-MSH - analogs & derivatives; Animals; Appetite, Obesity, Digestion; Body fat; Cricetinae; Herpesvirus 1, Suid; In Situ Hybridization; Male; Microinjections; Nervous system; Neurons; Neurons, Efferent - drug effects; Neurons, Efferent - metabolism; Paraventricular Hypothalamic Nucleus - metabolism; Peptides, Cyclic - administration & dosage; Phodopus; Receptor, Melanocortin, Type 4 - agonists; Receptor, Melanocortin, Type 4 - genetics; Receptor, Melanocortin, Type 4 - metabolism; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Rodents; Staining and Labeling - methods; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - metabolism; Thermogenesis - drug effects; Time Factors; Tissues
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00174.2008

1 Department of Biology and Center for Behavioral Neuroscience, Georgia State University, Atlanta; 2 Department of Foods and Nutrition, University of Georgia, Athens, Georgia; and 3 Centre 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 Address for reprint requests and other correspondence: T. J. Bartness, Dept. of Biology, Georgia State Univ., 24 Peachtree Center Ave. NE, Atlanta, GA 30302-4010 (e-mail: bartness{at}gsu.edu )