| First Author | Hondares E | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 50 | Pages | 43112-22 |
| PubMed ID | 22033933 | Mgi Jnum | J:178692 |
| Mgi Id | MGI:5299953 | Doi | 10.1074/jbc.M111.252775 |
| Citation | Hondares E, et al. (2011) Peroxisome Proliferator-activated Receptor alpha (PPARalpha) Induces PPARgamma Coactivator 1alpha (PGC-1alpha) Gene Expression and Contributes to Thermogenic Activation of Brown Fat: INVOLVEMENT OF PRDM16. J Biol Chem 286(50):43112-22 |
| abstractText | Peroxisome proliferator activated receptor alpha (PPARalpha) is a distinctive marker of the brown fat phenotype that has been proposed to coordinate the transcriptional activation of genes for lipid oxidation and for thermogenic uncoupling protein 1 in brown adipose tissue. Here, we investigated the involvement of PPARalpha in the transcriptional control of the PPARgamma coactivator (PGC)-1alpha gene. Treatment with PPARalpha agonists induced PGC-1alpha mRNA expression in brown fat in vivo and in primary brown adipocytes. This enhancement of PGC-1alpha transcription was mediated by PPARalpha binding to a PPAR-responsive element in the distal PGC-1alpha gene promoter. PGC-1alpha gene expression was decreased in PPARalpha-null brown fat, both under basal conditions and in response to thermogenic activation. Moreover, PPARalpha- and cAMP-mediated pathways interacted to control PGC-1alpha transcription. PRDM16 (PRD1-BF1-RIZ1 homologous domain-containing 16) promoted PPARalpha induction of PGC-1alpha gene transcription, especially under conditions in which protein kinase A pathways were activated. This enhancement was associated with the interaction of PRDM16 with the PGC-1alpha promoter at the PPARalpha-binding site. In addition, PPARalpha promoted the expression of the PRDM16 gene in brown adipocytes, and activation of PPARalpha in human white adipocytes led to the appearance of a brown adipocyte pattern of gene expression, including induction of PGC-1alpha and PRDM16. Collectively, these results suggest that PPARalpha acts as a key component of brown fat thermogenesis by coordinately regulating lipid catabolism and thermogenic gene expression via induction of PGC-1alpha and PRDM16. |
