Hondares, ElayneRosell, MeritxellDíaz Delfín, JulietaOlmos Buchelt, YolandaMonsalve, MaríaIglesias, RoserVillarroya, FrancescGiralt, Marta2024-07-012024-07-012011-10-27Hondares E, Rosell M, Díaz-Delfín J, Olmos Y, Monsalve M, Iglesias R, et al. Peroxisome Proliferator-activated Receptor α (PPARα) Induces PPARγ Coactivator 1α (PGC-1α) Gene Expression and Contributes to Thermogenic Activation of Brown Fat. Journal of Biological Chemistry. 2011;286(50):43112-220021-925810.1074/jbc.M111.252775https://hdl.handle.net/20.500.14352/105415Peroxisome proliferator activated receptor α (PPARα) 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 PPARα in the transcriptional control of the PPARγ coactivator (PGC)-1α gene. Treatment with PPARα agonists induced PGC-1α mRNA expression in brown fat in vivo and in primary brown adipocytes. This enhancement of PGC-1α transcription was mediated by PPARα binding to a PPAR-responsive element in the distal PGC-1α gene promoter. PGC-1α gene expression was decreased in PPARα-null brown fat, both under basal conditions and in response to thermogenic activation. Moreover, PPARα- and cAMP-mediated pathways interacted to control PGC-1α transcription. PRDM16 (PRD1-BF1-RIZ1 homologous domain-containing 16) promoted PPARα induction of PGC-1α 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-1α promoter at the PPARα-binding site. In addition, PPARα promoted the expression of the PRDM16 gene in brown adipocytes, and activation of PPARα in human white adipocytes led to the appearance of a brown adipocyte pattern of gene expression, including induction of PGC-1α and PRDM16. Collectively, these results suggest that PPARα acts as a key component of brown fat thermogenesis by coordinately regulating lipid catabolism and thermogenic gene expression via induction of PGC-1α and PRDM16.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1083-351Xhttps://doi.org/10.1074/jbc.M111.252775open access577.1577.2576Adipose TissueCyclic AMP (cAMP)DifferentiationObesityPeroxisome Proliferator-activated Receptor (PPAR)Protein Kinase A (PKA)Transcription CoactivatorsPGC-1PRDM16Brown Adipose TissueBiología molecular (Biología)Bioquímica (Biología)Biología celular (Biología)2415 Biología Molecular2403 Bioquímica2407 Biología Celular