Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation

Immunity. 2013 Jun 27;38(6):1154-63. doi: 10.1016/j.immuni.2013.05.015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Diabetes Mellitus, Type 2 / immunology
  • 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
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Receptors, G-Protein-Coupled / metabolism
  • beta-Arrestin 2
  • beta-Arrestins

Substances

  • ARRB2 protein, human
  • Arrb2 protein, mouse
  • Arrestins
  • Carrier Proteins
  • FFAR4 protein, mouse
  • Fatty Acids, Omega-3
  • Ffar1 protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Receptors, G-Protein-Coupled
  • beta-Arrestin 2
  • beta-Arrestins
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Caspase 1