title: Rosiglitazone-induced mitochondrial biogenesis in white adipose tissue is independent of peroxisome proliferator-activated receptor γ coactivator-1α.
abstract: BACKGROUND
  Thiazolidinediones, a family of insulin-sensitizing drugs commonly used to treat type 2 diabetes, are thought to exert their effects in part by promoting mitochondrial biogenesis in white adipose tissue through the transcriptional coactivator PGC-1α (Peroxisome Proliferator-Activated Receptor γ Coactivator-1α).
  
  
  RESULTS
  To assess the role of PGC-1α in the control of rosiglitazone-induced mitochondrial biogenesis, we have generated a mouse model that lacks expression of PGC-1α specifically in adipose tissues (PGC-1α-FAT-KO mice). We found that expression of genes encoding for mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation, was similar in white adipose tissue of wild type and PGC-1α-FAT-KO mice. Furthermore, the absence of PGC-1α did not prevent the positive effect of rosiglitazone on mitochondrial gene expression or biogenesis, but it precluded the induction by rosiglitazone of UCP1 and other brown fat-specific genes in white adipose tissue. Consistent with the in vivo findings, basal and rosiglitazone-induced mitochondrial gene expression in 3T3-L1 adipocytes was unaffected by the knockdown of PGC-1α but it was impaired when PGC-1β expression was knockdown by the use of specific siRNA.
  
  
  CONCLUSIONS
  These results indicate that in white adipose tissue PGC-1α is dispensable for basal and rosiglitazone-induced mitochondrial biogenesis but required for the rosiglitazone-induced expression of UCP1 and other brown adipocyte-specific markers. Our study suggests that PGC-1α is important for the appearance of brown adipocytes in white adipose tissue. Our findings also provide evidence that PGC-1β and not PGC-1α regulates basal and rosiglitazone-induced mitochondrial gene expression in white adipocytes.
authors.affiliation: Laboratory of Metabolism and Obesity, Unit of Diabetes and Metabolism, Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pardo
authors.forename: Natàlia
authors.initials: N
authors.lastname: Enguix
authors.forename: Jaime
authors.initials: J
authors.lastname: Lasheras
authors.forename: Juan E
authors.initials: JE
authors.lastname: Feliu
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kralli
authors.forename: Josep A
authors.initials: JA
authors.lastname: Villena
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034741:RNA, Small Interfering / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors
chemical_list: D007004:Hypoglycemic Agents; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; D000077154:Rosiglitazone
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