Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

• Published in: Biochemical and biophysical research communications Vol. 430; no. 1; pp. 225 - 230
• Main Authors: Kusunoki, Chisato, Yang, Liu, Yoshizaki, Takeshi, Nakagawa, Fumiyuki, Ishikado, Atsushi, Kondo, Motoyuki, Morino, Katsutaro, Sekine, Osamu, Ugi, Satoshi, Nishio, Yoshihiko, Kashiwagi, Atsunori, Maegawa, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.01.2013
• Subjects: 3T3-L1 Cells; 60 APPLIED LIFE SCIENCES; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; ADIPOSE TISSUE; Animals; antioxidants; Antioxidants - pharmacology; BENZOQUINONES; CATALASE; cytotoxicity; docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; Fatty Acids, Omega-3 - pharmacology; GLUTATHIONE; glutathione peroxidase; HEME; heme oxygenase (biliverdin-producing); Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - metabolism; HO-1; HYDROGEN PEROXIDE; INSULIN; insulin resistance; Membrane Proteins - biosynthesis; Membrane Proteins - metabolism; MESSENGER-RNA; METABOLIC DISEASES; METABOLITES; Mice; NAD; NF-E2-Related Factor 2 - biosynthesis; NF-E2-Related Factor 2 - metabolism; Nrf-2; omega-3 fatty acids; OXIDATION; Oxidative stress; Oxidative Stress - drug effects; OXIDIZERS; protein synthesis; SUPEROXIDE DISMUTASE; TETRAZOLIUM; TOXICITY; Water - pharmacology; ω3-Polyunsaturated fatty acid; NQO1; NBT; ω3-Polyunsaturated fatty acid; Oxidative stress; Nrf-2; HO-1; Adipocytes; Nrf2; EPA; ROS; DHA; ω3-PUFA; 4-HHE
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2012.10.115

► Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. ► EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. ► Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. ► Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. 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 H2O2-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.