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Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.
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.
Animals, Arrestins/metabolism, Carrier Proteins/genetics, Carrier Proteins/metabolism, Caspase 1/metabolism, Cells, Cultured, Diabetes Mellitus, Type 2/drug therapy, Diabetes Mellitus, Type 2/etiology, Diet, High-Fat/adverse effects, Docosahexaenoic Acids/pharmacology, Eicosapentaenoic Acid/pharmacology, Enzyme Activation/drug effects, Fatty Acids, Omega-3/immunology, Inflammasomes/immunology, Inflammasomes/metabolism, Inflammation/prevention & control, Interleukin-1beta/metabolism, Macrophages/drug effects, Macrophages/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, G-Protein-Coupled/metabolism
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