Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes
Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes
复制标题
DOI：
10.1016/j.bbrc.2012.10.115
复制
发表时间：
2013-01-04
影响因子：
3.1
通讯作者：
Maegawa, Hiroshi
中科院分区：
文献类型：
--
作者：
Kusunoki, Chisato;Yang, Liu;Maegawa, Hiroshi
氧化应激是在肥胖受试者的脂肪组织中产生的，并且与肥胖相关疾病有关。最近的研究表明，omega-3 多不饱和脂肪酸（omega-3-PUFA）对于预防动脉粥样硬化疾病和脂肪组织中的胰岛素抵抗具有有益作用。然而，omega 3-PUFA 对脂肪细胞的作用尚未阐明。在这项研究中，用 omega 3-PUFA 及其代谢物二十碳五烯酸 (EPA)、二十二碳六烯酸 (DHA) 或 4-羟基己烯醛 (4-HHE) 处理 3T3-L1 脂肪细胞。 omega 3-PUFA 及其代谢物剂量依赖性地增加抗氧化酶血红素加氧酶-1 (HO-1) 的 mRNA 和蛋白质水平；而众所周知的抗氧化剂分子、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶却没有观察到变化。核因子红细胞 2 相关因子 2 (Nrf-2) 的敲低显着降低了 EPA、DHA 或 4-HHE 诱导的 HO-1 mRNA 和蛋白质表达。此外，用 omega 3-PUFA 预处理可以以 HO-1 依赖性方式防止 H2O2 诱导的细胞毒性。总之，EPA 和 DHA 处理通过激活 Nrf-2 诱导 HO-1，并防止 3T3-L1 脂肪细胞中的氧化应激。这种抗氧化防御对于与全身氧化应激相关的临床病症可能具有很高的治疗价值。 (C) 2012 Elsevier Inc. 保留所有权利。
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 (omega 3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of omega 3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with omega 3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). omega 3-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 omega 3-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. (C) 2012 Elsevier Inc. All rights reserved.