title: Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation.
abstract: Brown adipocytes (BA) generate heat in response to sympathetic activation and are the main site of nonshivering thermogenesis in mammals. Although most BA are located in classic brown adipose tissue depots, BA are also abundant in the inguinal white adipose tissue (iWAT) before weaning. The number of BA is correlated with the density of sympathetic innervation in iWAT; however, the role of continuous sympathetic tone in the establishment and maintenance of BA in WAT has not been investigated. BA marker expression in iWAT was abundant in weaning mice but was greatly reduced by 8 wk of age. Nonetheless, BA phenotype could be rapidly reinstated by acute β₃-adrenergic stimulation with CL-316,243 (CL). Genetic tagging of adipocytes with adiponectin-CreER(T2) demonstrated that CL reinstates uncoupling protein 1 (UCP1) expression in adipocytes that were present before weaning. Chronic surgical denervation dramatically reduced the ability of CL to induce the expression of UCP1 and other BA markers in the tissue as a whole, and this loss of responsiveness was prevented by concurrent treatment with CL. These results indicate that ongoing sympathetic activity is critical to preserve the ability of iWAT fat cells to express a BA phenotype upon adrenergic stimulation.
authors.affiliation: Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan;
authors.forename: G Andres
authors.initials: GA
authors.lastname: Contreras
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University, Detroit, Michigan; and.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University, Detroit, Michigan; and.
authors.forename: Emilio P
authors.initials: EP
authors.lastname: Mottillo
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University, Detroit, Michigan; and Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan jgranne@med.wayne.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Granneman
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003433:Crosses, Genetic; D003714:Denervation / Q000009:adverse effects; D004149:Dioxoles / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006119:Groin; D007150:Immunohistochemistry; D007473:Ion Channels / Q000819:agonists / Q000378:metabolism; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000819:agonists / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology* / Q000254:growth & development / Q000294:innervation / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D000071256:Uncoupling Protein 1; D014886:Weaning
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D015415:Biomarkers; D004149:Dioxoles; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
keywords: inducible brown adipocytes; sympathetic innervation; uncoupling protein 1