title: Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic β3-adrenergic receptor activation.
abstract: Chronic activation of β3-adrenergic receptors (β3-ARs) expands the catabolic activity of both brown and white adipose tissue by engaging uncoupling protein 1 (UCP1)-dependent and UCP1-independent processes. The present work examined de novo lipogenesis (DNL) and TG/glycerol dynamics in classic brown, subcutaneous "beige," and classic white adipose tissues during sustained β3-AR activation by CL 316,243 (CL) and also addressed the contribution of TG hydrolysis to these dynamics. CL treatment for 7 days dramatically increased DNL and TG turnover similarly in all adipose depots, despite great differences in UCP1 abundance. Increased lipid turnover was accompanied by the simultaneous upregulation of genes involved in FAS, glycerol metabolism, and FA oxidation. Inducible, adipocyte-specific deletion of adipose TG lipase (ATGL), the rate-limiting enzyme for lipolysis, demonstrates that TG hydrolysis is required for CL-induced increases in DNL, TG turnover, and mitochondrial electron transport in all depots. Interestingly, the effect of ATGL deletion on induction of specific genes involved in FA oxidation and synthesis varied among fat depots. Overall, these studies indicate that FAS and FA oxidation are tightly coupled in adipose tissues during chronic adrenergic activation, and this effect critically depends on the activity of adipocyte ATGL.
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Emilio P
authors.initials: EP
authors.lastname: Mottillo
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Priya
authors.initials: P
authors.lastname: Balasubramanian
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Changren
authors.initials: C
authors.lastname: Weng
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Kershaw
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI.
authors.forename: James G
authors.initials: JG
authors.lastname: Granneman
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D005990:Glycerol / Q000378:metabolism; D007700:Kinetics; D008049:Lipase / Q000172:deficiency / Q000235:genetics; D050155:Lipogenesis / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D004149:Dioxoles; D005990:Glycerol; D008049:Lipase; D022702:Receptors, Adrenergic, beta-3; D014280:Triglycerides; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: adipose triglyceride lipase; lipid synthesis; tamoxifen-inducible Cre recombinase (Adipoq-CreERT2); uncoupling protein 1