title: Dietary Effects of Oxidized Eicosapentaenoic Acid (EPA) and Intact EPA on Hepatic Steatosis Induced by a High-sucrose Diet and Liver-X-receptor α Agonist in Mice.
abstract: Numerous studies have shown that dietary omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA), improve lipid metabolism. The beneficial effects of PUFA-derived oxidation products have been increasingly reported. However, EPA is easily oxidized in food products and in the human body, generating various derivatives of oxidized EPA (oxEPA), such that these oxidation products may partially contribute to EPA's effect. We previously reported that oxEPA was more potent than intact EPA in reducing liver-X-receptor α (LXRα)-induced cellular triacylglycerol (TG) accumulation. However, the in vivo hypolipidemic effects of oxEPA remain unclear. In the present study, we evaluated the effect of oral administration of EPA and oxEPA on hepatic steatosis in mice induced by a high-sucrose diet and a synthetic LXRα agonist, TO-901317. Both EPA and oxEPA reduced TG accumulation in the liver and plasma biomarkers of liver injury. Furthermore, they suppressed the expression of lipogenic genes, but not β-oxidation genes, in a similar pattern as the biomarkers. Our results suggest that oxEPA and intact EPA suppress de novo lipogenesis to ameliorate hepatic steatosis.
authors.affiliation: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Furumoto
authors.forename: Tharnath
authors.initials: T
authors.lastname: Nanthirudjanar
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sugawara
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D019422:Dietary Sucrose / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects*; D000960:Hypolipidemic Agents; D050155:Lipogenesis / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors / Q000819:agonists*; D008297:Male; D008813:Mice, Inbred ICR; D010084:Oxidation-Reduction; D013449:Sulfonamides / Q000009:adverse effects*; D014280:Triglycerides / Q000378:metabolism*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D015415:Biomarkers; D019422:Dietary Sucrose; D015118:Eicosapentaenoic Acid; D006845:Hydrocarbons, Fluorinated; D000960:Hypolipidemic Agents; D000071518:Liver X Receptors; D013449:Sulfonamides; D014280:Triglycerides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides