Increased oxidative stress in obesity and its impact on metabolic syndrome

被引:3594
作者
Furukawa, S
Fujita, T
Shimabukuro, M
Iwaki, M
Yamada, Y
Nakajima, Y
Nakayama, O
Makishima, M
Matsuda, M
Shimomura, I
机构
[1] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Frontier Biosci, Dept Organismal Biosyst, Grad Sch Med,Dept Med & Pathophysiol, Suita, Osaka 5650871, Japan
[3] Univ Ryukyus, Dept Internal Med 2, Okinawa, Japan
[4] Fujisawa Pharmaceut Co Ltd, Exploratory Res Labs, Tsukuba, Ibaraki 30026, Japan
[5] Japan Sci & Technol Corp, PRESTO, Kawaguchi, Saitama, Japan
关键词
D O I
10.1172/JCI20042162S
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:1752 / 1761
页数:10
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