Differential action of 13-HPODE on PPARα downstream genes in rat Fao and human HepG2 hepatoma cell lines

In rats, oxidized fats activate the peroxisome proliferator-activated receptor alpha (PPAR alpha), leading to reduced triglyceride concentrations in liver, plasma and very low density lipoproteins. Oxidation products of linoleic acid constitute an important portion of oxidized dietary fats. This study was conducted to check whether the primary lipid peroxidation product of linoleic acid, 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE), might be involved in the PPAR alpha-activating effect of oxidized fats. Therefore, we examined the effect of 13-HPODE on the expression of PPARa target genes in the rat Fao and the human HepG2 hepatoma cell lines. In Fao cells, 13-HPODE increased the mRNA concentration of the PPAR alpha target genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 and camitine-palmitoyltransferase 1A (CPT1A). Furthermore, the concentration of cellular and secreted triglycerides was reduced in Fao cells treated with 13-HPODE. Because PPAR alpha mRNA was not influenced, we conclude that these effects are due to an activation of PPAR alpha by 13-HPODE. In contrast, HepG2 cells seemed to be resistant to PPAR alpha activation by 13-HPODE because no remarkable induction of the PPAR(x target genes ACO, CPTIA, mitochondrial HMG-CoA synthase and Delta 9-desaturase was observed. Consequently, cellular and secreted triglyceride levels were not changed after incubation of HepG2 cells with 13-HPODE. In conclusion, this study shows that 13-HPODE activates PPAR alpha in rat Fao but not in human HepG2 hepatoma cells. (c) 2006 Elsevier Inc. All rights reserved.