Ligand- and Species-Dependent Activation of PPARα
Peroxisome proliferator-activated receptor alpha (PPARα) is mainly expressed in liver and involved in lipid metabolism. Oxidation of certain fatty acids in peroxisomes is under PPARα control. A wide variety of lipid molecules activate PPARα as well as the fibric acid derivative clofibrate. In the present study, we evaluated the differential activation of PPARα with several agonist ligands through its expression and DNA binding in both rat (McA-RH7777) and human (HepG2) hepatoma cell lines. In McA-RH7777 cells, clofibrate alone mediated a higher induction of PPARα expression than linoleic acid. In contrast, linoleic acid was the most effective ligand in HepG2 cells and treatment with clofibrate plus linoleic acid did not further increase PPARα expression. PPRE-binding activity of PPARα in ligand-treated cells was also increased in a parallel manner. We suggest that ligand-induced PPARα activation might give rise to differential species-dependent responses.