title: A peroxisome proliferator-activated receptor gamma (PPARgamma)/PPARgamma coactivator 1beta autoregulatory loop in adipocyte mitochondrial function.
abstract: Peroxisome proliferator-activated receptor γ (PPARγ) activation induces adipogenesis and also enhances lipogenesis, mitochondrial activity, and insulin sensitivity in adipocytes. Whereas some studies implicate PPARγ coactivator 1α (PGC-1α) in the mitochondrial effect, the mechanisms involved in PPARγ regulation of adipocyte mitochondrial function are not resolved. PPARγ-activating ligands (thiazolidinediones (TZDs)) are important insulin sensitizers and were recently shown to indirectly induce PGC-1β transcription in osteoclasts. Here, we asked whether similar effects occur in adipocytes and show that TZDs also strongly induce PGC-1β in cultured 3T3-L1 cells. This effect, however, differs from the indirect effect proposed for bone and is rapid and direct and involves PPARγ interactions with an intronic PPARγ response element cluster in the PGC-1β locus. TZD treatment of cultured adipocytes results in up-regulation of mitochondrial marker genes, and increased mitochondrial activity and use of short interfering RNA confirms that these effects require PGC-1β. PGC-1β did not participate in PPARγ effects on adipogenesis or lipogenesis, and PGC-1β knockdown did not alter insulin-responsive glucose uptake into 3T3-L1 cells. Similar effects on PGC-1β and mitochondrial gene expression are seen in vivo; fractionation of obese mouse adipose tissue reveals that PPARγ and PGC-1β, but not PGC-1α, are coordinately up-regulated in adipocytes relative to preadipocytes and that TZD treatment induces PGC-1β and mitochondrial marker genes in adipose tissue of obese mice. We propose that PPARγ directly induces PGC-1β expression in adipocytes and that this effect regulates adipocyte mitochondrial activity.
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Tuo
authors: T
authors: Deng
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Douglas H
authors: DH
authors: Sieglaff
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Aijun
authors: A
authors: Zhang
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Christopher J
authors: CJ
authors: Lyon
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Steven D
authors: SD
authors: Ayers
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Aleksandra
authors: A
authors: Cvoro
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Anisha A
authors: AA
authors: Gupte
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Xuefeng
authors: X
authors: Xia
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: John D
authors: JD
authors: Baxter
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030.
authors: Paul
authors: P
authors: Webb
authors: Methodist Hospital Research Institute, Center for Diabetes Research, Weill Cornell Medical College, The Methodist Hospital, Houston, Texas 77030. Electronic address: wahsueh@tmhs.org.
authors: Willa A
authors: WA
authors: Hsueh
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010101:Oxygen Consumption; D047495:PPAR gamma / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D045162:Thiazolidinediones / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D005227:Fatty Acids; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors