| First Author | Kim J | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 7 | Pages | e0159990 |
| PubMed ID | 27454177 | Mgi Jnum | J:249151 |
| Mgi Id | MGI:6094737 | Doi | 10.1371/journal.pone.0159990 |
| Citation | Kim J, et al. (2016) Regulation of Brown and White Adipocyte Transcriptome by the Transcriptional Coactivator NT-PGC-1alpha. PLoS One 11(7):e0159990 |
| abstractText | The beta3-adrenergic receptor (AR) signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The beta3-AR signaling highly induces the expression of transcriptional coactivator PGC-1alpha and its splice variant N-terminal (NT)-PGC-1alpha, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of transcription factors. We previously reported that NT-PGC-1alpha is able to increase mitochondrial number and activity in cultured brown adipocytes by promoting the expression of mitochondrial and thermogenic genes. In the present study, we performed genome-wide profiling of NT-PGC-1alpha-responsive genes in brown adipocytes to identify genes potentially regulated by NT-PGC-1alpha. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1alpha are highly enriched in mitochondrial pathways including fatty acid transport and beta-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1alpha in the enhancement of mitochondrial function. Moreover, canonical pathway analysis of NT-PGC-1alpha-responsive genes identified several metabolic pathways including glycolysis and fatty acid synthesis. In order to validate the identified genes in vivo, we utilized the FL-PGC-1alpha-/- mouse that is deficient in full-length PGC-1alpha (FL-PGC-1alpha) but expresses a slightly shorter and functionally equivalent form of NT-PGC-1alpha (NT-PGC-1alpha254). The beta3-AR-induced increase of NT-PGC-1alpha254 in FL-PGC-1alpha-/- brown and white adipose tissue was closely associated with elevated expression of genes involved in thermogenesis, mitochondrial oxidative metabolism, glycolysis and fatty acid synthesis. Increased adipose tissue thermogenesis by beta3-AR activation resulted in attenuation of adipose tissue expansion in FL-PGC-1alpha-/- adipose tissue under the high-fat diet condition. Together, the data strengthen our previous findings that NT-PGC-1alpha regulates mitochondrial genes involved in thermogenesis and oxidative metabolism in brown and white adipocytes and further suggest that NT-PGC-1alpha regulates a broad spectrum of genes to meet cellular needs for adaptive thermogenesis. |
