title: Dietary fatty acid composition is sensed by the NLRP3 inflammasome: omega-3 fatty acid (DHA) prevents NLRP3 activation in human macrophages.
abstract: The Nod-like receptor protein 3 (NLRP3) inflammasome is considered to be a pivotal host platform responsible for sensing of exogenous and endogenous danger signals, including those generated as a result of metabolic dysregulation, and for the subsequent, IL-1β-mediated orchestration of inflammatory and innate immunity responses. In this way, although the molecular link between diet-induced obesity and inflammasome activation is still unclear, free fatty acids (FFA) have been proposed as a triggering event. We report that dietary fatty acid (FA) composition is sensed by the NLRP3 inflammasome in human macrophages. For this purpose, we have analysed three roles of FA supplementation: as a priming signal for ATP-activated macrophages, in determining where the administration of dietary FAs interferes with LPS-mediated inflammasome activation and by inducing inflammasome activation per se. In this study, we confirm that saturated (SFAs) activated the NLRP3 inflammasome and stimulated the secretion of the IL-1β cytokine, while PUFAs were mainly inhibitors. Moreover, in general, DHA (n-3 PUFA) was more effective in preventing inflammasome activation than arachidonic acid (n-6 PUFA).
authors.affiliation: Mobiofood Research Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona, Spain. mteresa.blay@urv.cat.
authors.forename: N
authors.initials: N
authors.lastname: Martínez-Micaelo
authors.forename: N
authors.initials: N
authors.lastname: González-Abuín
authors.forename: M
authors.initials: M
authors.lastname: Pinent
authors.forename: A
authors.initials: A
authors.lastname: Ardévol
authors.forename: M
authors.initials: M
authors.lastname: Blay
mesh_terms: D016718:Arachidonic Acid / Q000008:administration & dosage; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004032:Diet; D019587:Dietary Supplements; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D058847:Inflammasomes / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy; D000074084:THP-1 Cells
chemical_list: D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D058847:Inflammasomes; D007375:Interleukin-1; D053583:Interleukin-1beta; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D016718:Arachidonic Acid; D020170:Caspase 1