title: Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes.
abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid (ω3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of ω3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with ω3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). ω3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with ω3-PUFA prevented H(2)O(2)-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192, Japan. yosizaki@belle.shiga-med.ac.jp
authors.forename: Chisato
authors.initials: C
authors.lastname: Kusunoki
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Nakagawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishikado
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kondo
authors.forename: Katsutaro
authors.initials: K
authors.lastname: Morino
authors.forename: Osamu
authors.initials: O
authors.lastname: Sekine
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ugi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nishio
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D014867:Water / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D014867:Water; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse