| First Author | Pardo R | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 11 | Pages | e26989 |
| PubMed ID | 22087241 | Mgi Jnum | J:180984 |
| Mgi Id | MGI:5308501 | Doi | 10.1371/journal.pone.0026989 |
| Citation | Pardo R, et al. (2011) Rosiglitazone-induced mitochondrial biogenesis in white adipose tissue is independent of peroxisome proliferator-activated receptor gamma coactivator-1alpha. PLoS One 6(11):e26989 |
| abstractText | 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-1alpha (Peroxisome Proliferator-Activated Receptor gamma Coactivator-1alpha). METHODOLOGY/PRINCIPAL FINDINGS: To assess the role of PGC-1alpha in the control of rosiglitazone-induced mitochondrial biogenesis, we have generated a mouse model that lacks expression of PGC-1alpha specifically in adipose tissues (PGC-1alpha-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-1alpha-FAT-KO mice. Furthermore, the absence of PGC-1alpha 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-1alpha but it was impaired when PGC-1beta expression was knockdown by the use of specific siRNA. CONCLUSIONS/SIGNIFICANCE: These results indicate that in white adipose tissue PGC-1alpha 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-1alpha is important for the appearance of brown adipocytes in white adipose tissue. Our findings also provide evidence that PGC-1beta and not PGC-1alpha regulates basal and rosiglitazone-induced mitochondrial gene expression in white adipocytes. |
