title: Metabolic heterogeneity of activated beige/brite adipocytes in inguinal adipose tissue.
abstract: Sustained β3 adrenergic receptor (ADRB3) activation simultaneously upregulates fatty acid synthesis and oxidation in mouse brown, beige, and white adipose tissues; however, the cellular basis of this dual regulation is not known. Treatment of mice with the ADRB3 agonist CL316,243 (CL) increased expression of fatty acid synthase (FASN) and medium chain acyl-CoA dehydrogenase (MCAD) protein within the same cells in classic brown and white adipose tissues. Surprisingly, in inguinal adipose tissue, CL-upregulated FASN and MCAD in distinct cell populations: high MCAD expression occurred in multilocular adipocytes that co-expressed UCP1+, whereas high FASN expression occurred in paucilocular adipocytes lacking detectable UCP1. Genetic tracing with UCP1-cre, however, indicated nearly half of adipocytes with a history of UCP1 expression expressed high levels of FASN without current expression of UCP1. Global transcriptomic analysis of FACS-isolated adipocytes confirmed the presence of distinct anabolic and catabolic phenotypes, and identified differential expression of transcriptional pathways known to regulate lipid synthesis and oxidation. Surprisingly, paternally-expressed genes of the non-classical gene imprinted network were strikingly enriched in anabolic phenotypes, suggesting possible involvement in maintaining the balance of metabolic phenotypes. The results indicate that metabolic heterogeneity is a distinct property of activated beige/brite adipocytes that might be under epigenetic control.
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.
authors.forename: Sang-Nam
authors.initials: SN
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Granneman
mesh_terms: D050153:Abdominal Fat / Q000166:cytology / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D000069796:Adipose Tissue, Beige / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D044127:Epigenesis, Genetic; D064429:Fatty Acid Synthases / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010641:Phenotype; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D059467:Transcriptome; D000071256:Uncoupling Protein 1
chemical_list: C000627368:Adrb3 protein, mouse; D022702:Receptors, Adrenergic, beta-3; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D042964:Acyl-CoA Dehydrogenase; D064429:Fatty Acid Synthases