Omega-3 Fatty Acids Prevent Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome Activation
Omega-3 Fatty Acids Prevent Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome Activation
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Omega-3 脂肪酸通过抑制 NLRP3 炎症小体激活来预防炎症和代谢紊乱。
DOI：
10.1016/j.immuni.2013.05.015
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发表时间：
2013-06-27
期刊：
影响因子：
32.4
通讯作者：
Zhou, Rongbin
中科院分区：
文献类型：
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作者：
Yan, Yiqing;Jiang, Wei;Zhou, Rongbin
ω-3脂肪酸（ω-3 FAs）在多种炎症性人类疾病中具有潜在的抗炎活性，但其机制仍知之甚少。在这里，我们表明，刺激巨噬细胞与ω-3脂肪酸，包括二十碳五烯酸（EPA），二十二碳六烯酸（DHA），和其他家庭成员，废除NLRP 3炎性小体激活和抑制随后的半胱天冬酶-1激活和IL-1 β分泌。此外，G蛋白偶联受体120（GPR 120）和GPR 40及其下游支架蛋白β-arrestin-2被证明参与omega-3 FA诱导的炎性小体抑制。重要的是，u-3 FA还预防了高脂饮食诱导的2型糖尿病模型中的NLRP 3炎性体依赖性炎症和代谢紊乱。我们的结果揭示了u-3FA抑制炎症和预防炎症驱动的疾病的机制，并表明ω-3FA在痛风、自身炎性综合征或其他NLRP 3炎性小体驱动的炎性疾病中的潜在临床用途。
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.