Omega-3 Fatty Acids Prevent Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome Activation

被引：632

作者：

Yan, Yiqing ^{[1
,2
]}

Jiang, Wei ^{[1
,2
]}

Spinetti, Thibaud ^{[3
,4
]}

Tardivel, Aubry ^{[3
]}

Castillo, Rosa ^{[3
]}

Bourquin, Carole ^{[4
]}

Guarda, Greta ^{[3
]}

Tian, Zhigang ^{[1
,2
]}

Tschopp, Jurg ^{[3
]}

Zhou, Rongbin ^{[1
,2
]}

机构：

[1] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China

[2] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China

[3] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[4] Univ Fribourg, Dept Med, Chair Pharmacol, CH-1700 Fribourg, Switzerland

来源：

IMMUNITY | 2013年 / 38卷 / 06期

基金：

国家教育部博士点专项基金资助; 瑞士国家科学基金会; 欧盟第七框架计划;

关键词：

POLYUNSATURATED FATTY-ACIDS; TUMOR-NECROSIS-FACTOR; INSULIN-SECRETION; OXIDATIVE STRESS; TRANSGENIC MICE; INTERLEUKIN-1; DYSFUNCTION; RESOLVINS; MEDIATORS; INTERACTS;

D O I：

10.1016/j.immuni.2013.05.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Omega-3 fatty acids (omega-3 FAs) have potential antiinflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with omega-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1 beta secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein beta-arrestin-2 were shown to be involved in inflammasome inhibition induced by omega-3 FAs. Importantly, u-3 FAs also prevented NLRP3 inflammasomedependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which u-3 FAs repress inflammation and prevent inflammation- driven diseases and suggest the potential clinical use of omega-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases.

引用

页码：1154 / 1163

页数：10

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