Rosiglitazone-Induced Mitochondrial Biogenesis in White Adipose Tissue Is Independent of Peroxisome Proliferator-Activated Receptor γ Coactivator-1α
Pardo, Rosario (Hospital Universitari Vall d'Hebron)
Enguix, Natàlia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lasheras Márquez, Jaime (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Feliu Albiñana, Juan Emilio (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Kralli, Anastasia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Villena, Josep A. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2011
Resum:	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). 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. 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.
Ajuts:	Ministerio de Ciencia e Innovación SAF2008-03644 Ministerio de Ciencia e Innovación RYC-2006-00262 Ministerio de Ciencia e Innovación BES-2009-013411
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 6 (november 2011) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0026989
PMID: 22087241

13 p, 812.4 KB

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