title: NLRP3 at the interface of metabolism and inflammation.
abstract: The discovery of the NLRP3 (NLR family, pyrin domain containing 3) inflammasome provided an important molecular mechanism in the induction of the central pro-inflammatory cytokine interleukin-1β (IL-1β), via activation of caspase-1, which processes pro-IL-1β into its mature active form. IL-1 has long been known to exert metabolic effects, most notably being implicated in insulin resistance and obesity. A key phenotype of the NLRP3-deficient mouse is insulin hypersensitivity. Over the past 5 years, a number of discoveries have been made suggesting a close interplay between NLRP3 and metabolism. Metabolic products have been shown to activate NLPR3, and disturbed mitochondria have been shown to be involved in NLRP3 function. It is possible that under normal physiology NLRP3 is homeostatic and maintains the metabolic balance. However, upon chronic activation (e.g. in obesity or hypercholesterolemia), NLRP3 becomes pathologic and promotes disease. Here, we review these findings and place them in the context of exciting new insights that are improving our understanding of the link between inflammation and metabolism. These insights are giving rise to better understanding of disease pathogenesis and might point to new therapeutic approaches.
authors: School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors: Moritz
authors: M
authors: Haneklaus
authors: Luke A J
authors: LA
authors: O'Neill
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000276:immunology / Q000378:metabolism*; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000276:immunology / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse
keywords: IL-1; NLRP3; inflammasome; metabolism