Oxidized frying oil up-regulates hepatic acyl-CoA oxidase and cytochrome P450 4 A1 genes in rats and activates PPARα

Oxidized LDL (oxLDL) and its component hydroxy fatty acids were shown to activate peroxisome proliferator-activating receptor alpha (PPAR alpha) and gamma (PPAR gamma). To test the hypothesis that lipid oxidation products in oxidized frying oil (OFO) can activate PPAR alpha and up-regulate its target genes, a feeding experiment and a transactivation experiment were conducted. Based on a 2 x 2 factorial design, four groups of Sprague-Dawley male weanling rats were fed diets containing either high (20 g/100 g, HO and HF) or low (5 g/100 g, LO and LF) levels of oxidized frying soybean oil (HO and LO) or fresh soybean oil (HF and LF) for 6 wk. The OFO sample was prepared by frying wheat dough sheets in soybean oil at 205 +/- 5 degreesC for 24 h. OFO dose dependently and significantly increased (P < 0.05) mRNA of acyl-CoA oxidase (ACO) and cytochrome P-450 4A1(CYP4A1) in liver of rats. Dietary OFO also dose dependently increased liver microsomal CYP4A protein (P < 0.05). The activity of hepatic ACO of the HO group was sixfold that of the HF group (P < 0.05). Plasma total lipids, liver triglycerides, cholesterol and total lipids were reduced in rats fed the LO and HO diets (P < 0.05). Through the ligand binding domain of PPAR alpha, the hydrolyzed OFO enhanced the expression of alkaline phosphatase (ALP) reporter gene to a significantly greater extent (P < 0.05) than the hydrolyzed fresh soybean oil in a transactivation assay using a clone of CHO K1 cells stably expressing Gal4-PPAR<alpha> chimeric receptor and UAS(4)-ALP reporter. The results support our hypothesis that dietary OFO, by activating PPAR alpha, up-regulates the expression of PPAR alpha downstream genes and alters lipid metabolism in rats.