Oxidized frying oil up-regulates hepatic acyl-CoA oxidase and cytochrome P450 4 A1 genes in rats and activates PPARalpha.
Oxidized LDL (oxLDL) and its component hydroxy fatty acids were shown to activate peroxisome proliferator-activating receptor alpha (PPARalpha) and gamma (PPARgamma). To test the hypothesis that lipid oxidation products in oxidized frying oil (OFO) can activate PPARalpha 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 degrees C 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 PPARalpha, 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-PPARalpha chimeric receptor and UAS4-ALP reporter. The results support our hypothesis that dietary OFO, by activating PPARalpha, up-regulates the expression of PPARalpha downstream genes and alters lipid metabolism in rats.
Chao
P M
PM
Laboratory of Nutritional Biochemistry, Department of Agricultural Chemistry, National Taiwan University, Taipei 106, Taiwan.
Chao
C Y
CY
Lin
F J
FJ
Huang
C
C
D042962:Acyl-CoA Oxidase; D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004268:DNA-Binding Proteins; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006868:Hydrolysis; D007668:Kidney / Q000201:enzymology; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics*; D020675:Peroxisomes / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013024:Soybean Oil / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014280:Triglycerides / Q000378:metabolism; D014886:Weaning
D004268:DNA-Binding Proteins; D004042:Dietary Fats, Unsaturated; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D008054:Lipid Peroxides; D008055:Lipids; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D013024:Soybean Oil; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D002374:Catalase; D042926:Cytochrome P-450 CYP4A; D042962:Acyl-CoA Oxidase; D000469:Alkaline Phosphatase