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

Author: Y Yan, et al
Source: Immunity, Volume 38, Issue 6, 1154-1163, 27 June 2013
Publication Date: 6/27/2013

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Omega-3 fatty acids (-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 -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-1ß secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein ß-arrestin-2 were shown to be involved in inflammasome inhibition induced by -3 FAs. Importantly, -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 -3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of -3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases.