Differential action of 13-HPODE on PPARalpha downstream genes in rat Fao and human HepG2 hepatoma cell lines.
In rats, oxidized fats activate the peroxisome proliferator-activated receptor alpha (PPARalpha), 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 PPARalpha-activating effect of oxidized fats. Therefore, we examined the effect of 13-HPODE on the expression of PPARalpha target genes in the rat Fao and the human HepG2 hepatoma cell lines. In Fao cells, 13-HPODE increased the mRNA concentration of the PPARalpha target genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 and carnitine-palmitoyltransferase 1A (CPT1A). Furthermore, the concentration of cellular and secreted triglycerides was reduced in Fao cells treated with 13-HPODE. Because PPARalpha mRNA was not influenced, we conclude that these effects are due to an activation of PPARalpha by 13-HPODE. In contrast, HepG2 cells seemed to be resistant to PPARalpha activation by 13-HPODE because no remarkable induction of the PPARalpha target genes ACO, CPT1A, mitochondrial HMG-CoA synthase and delta9-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 PPARalpha in rat Fao but not in human HepG2 hepatoma cells.
König
Bettina
B
Institut für Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, D-06108 Halle (Saale), Germany. bettina.koenig@landw.uni-halle.de
Eder
Klaus
K
D042962:Acyl-CoA Oxidase / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D045744:Cell Line, Tumor; D042926:Cytochrome P-450 CYP4A / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008054:Lipid Peroxides / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008113:Liver Neoplasms; D008114:Liver Neoplasms, Experimental; D047493:PPAR alpha / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
D008041:Linoleic Acids; D008054:Lipid Peroxides; D008055:Lipids; D047493:PPAR alpha; D012333:RNA, Messenger; D014280:Triglycerides; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D019787:Linoleic Acid; D042926:Cytochrome P-450 CYP4A; D042962:Acyl-CoA Oxidase; D002334:Carnitine O-Palmitoyltransferase