TY - JOUR A2 - Glauert, Howard P. AU - Bigo, Cyril AU - Kaeding, Jenny AU - El Husseini, Diala AU - Rudkowska, Iwona AU - Verreault, Mélanie AU - Vohl, Marie Claude AU - Barbier, Olivier PY - 2014 DA - 2014/07/23 TI - PPARα: A Master Regulator of Bilirubin Homeostasis SP - 747014 VL - 2014 AB - Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin synthesizing heme oxygenase- (HO-) 1 and biliverdin reductase (BVR) enzymes were determined. Human hepatocytes (HH) and HepG2 cells sustained similar treatments, except that the expression of the bilirubin conjugating UDP-glucuronosyltransferase (UGT) 1A1 enzyme and multidrug resistance-associated protein (MRP) 2 transporter was analyzed. In HUVECs, gemfibrozil, fenofibrate, and Wy14,643 upregulated HO-1 mRNA expression without affecting BVR. Wy14,643 and fenofibrate also caused HO-1 protein accumulation, while gemfibrozil and fenofibrate favored the secretion of bilirubin in cell media. Similar positive regulations were also observed with the 3 PPARα ligands in CASMCs where HO-1 mRNA and protein levels were increased. In HH and HepG2 cells, both UGT1A1 and MRP2 transcripts were also accumulating. These observations indicate that PPARα ligands activate bilirubin synthesis in vascular cells and metabolism in liver cells. The clinical implications of these regulatory events are discussed. SN - 1687-4757 UR - https://doi.org/10.1155/2014/747014 DO - 10.1155/2014/747014 JF - PPAR Research PB - Hindawi Publishing Corporation KW - ER -