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

• Published in: Immunity (Cambridge, Mass.) Mass.), 2013-06, Vol.38 (6), p.1154-1163
• Main Authors: Yan, Yiqing, Jiang, Wei, Spinetti, Thibaud, Tardivel, Aubry, Castillo, Rosa, Bourquin, Carole, Guarda, Greta, Tian, Zhigang, Tschopp, Jurg, Zhou, Rongbin
• Format: Article
• Language: English
• Subjects: Animals; Arrestins - metabolism; beta-Arrestin 2; beta-Arrestins; Carrier Proteins - genetics; Carrier Proteins - metabolism; Caspase 1 - metabolism; Cells, Cultured; Cytokines; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - immunology; Diet, High-Fat - adverse effects; Docosahexaenoic Acids - pharmacology; Eicosapentaenoic Acid - pharmacology; Enzyme Activation - drug effects; Fatty acids; Fatty Acids, Omega-3 - immunology; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation - prevention & control; Interleukin-1beta - metabolism; Macrophages - drug effects; Macrophages - immunology; Metabolic disorders; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Receptors, G-Protein-Coupled - metabolism; Studies
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.05.015

Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-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-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases. •ω-3 FAs inhibit NLRP3 inflammasome activation•β-arrestin-2 is involved in ω-3 FAs-induced inflammasome inhibition•ω-3 FAs inhibit HFD-induced NLRP3 inflammasome activation in vivo•ω-3 FAs prevent HFD-induced metabolic disorder via inhibition of NLRP3 inflammasome