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

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.