PathwayStep1354 PathwayStep1355 PathwayStep1397 PathwayStep1353 Recruitment of Corepressors by PPARA:RXRA Heterodimer Activation of PPARA by Fatty Acid Ligands Formation of PPARA:RXRA Heterodimer at Promoters of Target Genes PPARA Activates Gene Expression Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) Authored: May, B, 2009-05-30 16:45:51 Edited: May, B, 2009-05-30 16:45:51 Edited: May, B, 2009-06-08 Edited: May, B, 2011-11-08 Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma lipid levels. <br>PPAR-alpha is a type II nuclear receptor (its subcellular location does not depend on ligand binding). PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha), another type II nuclear receptor. PPAR-alpha is activated by binding fatty acid ligands, especially polyunsaturated fatty acids having 18-22 carbon groups and 2-6 double bonds. <br>The PPAR-alpha:RXR-alpha heterodimer binds peroxisome proliferator receptor elements (PPREs) in and around target genes. Binding of fatty acids and synthetic ligands causes a conformational change in PPAR-alpha such that it releases the corepressors and binds coactivators (CBP-SRC-HAT complex, ASC complex, and TRAP-Mediator complex) which initiate transcription of the target genes.<br>Target genes of PPAR-alpha participate in fatty acid transport, fatty acid oxidation, triglyceride clearance, lipoprotein production, and cholesterol homeostasis. Pubmed10529898 Pubmed16476485 Pubmed16503871 Pubmed18288277 Reactome Database ID Release 43400206 Reactome, http://www.reactome.org ReactomeREACT_19241 Reviewed: Kersten, S, 2009-06-08