Increased oxidative stress in obesity and its impact on metabolic syndrome.
Increased oxidative stress in obesity and its impact on metabolic syndrome.
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DOI：
10.1172/jci21625
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发表时间：
2004-01-01
影响因子：
15.9
通讯作者：
Shimomura, I.
中科院分区：
文献类型：
--
作者：
Furukawa, S.;Fujita, T.;Shimomura, I.
肥胖是代谢综合征的主要致病因素。在这里，我们报告说，增加氧化应激积累的脂肪是一个重要的致病机制肥胖相关的代谢综合征。脂肪蓄积与人类和小鼠的全身氧化应激相关。肥胖小鼠脂肪组织中活性氧的产生选择性增加，同时伴有NADPH氧化酶表达增加和抗氧化酶表达减少。在培养的脂肪细胞中，脂肪酸水平升高通过NADPH氧化酶激活增加氧化应激，氧化应激引起脂肪细胞因子（脂肪源性激素），包括脂联素，纤溶酶原激活物抑制剂-1，IL-6和单核细胞趋化蛋白-1的生产失调。最后，在肥胖小鼠中，用NADPH氧化酶抑制剂治疗减少了脂肪组织中ROS的产生，减弱了脂肪细胞因子的失调，并改善了糖尿病、高脂血症和肝脂肪变性。总的来说，我们的研究结果表明，在积累的脂肪中增加氧化应激是代谢综合征的早期诱因，脂肪组织中的氧化还原状态是肥胖相关代谢综合征的潜在有用的治疗靶点。
Obesity is a principal causative factor in the development of metabolic syndrome. Here we report that increased oxidative stress in accumulated fat is an important pathogenic mechanism of obesity-associated metabolic syndrome. Fat accumulation correlated with systemic oxidative stress in humans and mice. Production of ROS increased selectively in adipose tissue of obese mice, accompanied by augmented expression of NADPH oxidase and decreased expression of antioxidative enzymes. In cultured adipocytes, elevated levels of fatty acids increased oxidative stress via NADPH oxidase activation, and oxidative stress caused dysregulated production of adipocytokines (fat-derived hormones), including adiponectin, plasminogen activator inhibitor-1, IL-6, and monocyte chemotactic protein-1. Finally, in obese mice, treatment with NADPH oxidase inhibitor reduced ROS production in adipose tissue, attenuated the dysregulation of adipocytokines, and improved diabetes, hyperlipidemia, and hepatic steatosis. Collectively, our results suggest that increased oxidative stress in accumulated fat is an early instigator of metabolic syndrome and that the redox state in adipose tissue is a potentially useful therapeutic target for obesity-associated metabolic syndrome.