NLRP3 at the interface of metabolism and inflammation

<jats:title>Summary</jats:title><jats:p>The discovery of the <jats:styled-content style="fixed-case">NLRP</jats:styled-content>3 (<jats:styled-content style="fixed-case">NLR</jats:styled-content> family, pyrin domain containing 3) inflammasome provided an important molecular mechanism in the induction of the central pro‐inflammatory cytokine interleukin‐1β (<jats:styled-content style="fixed-case">IL</jats:styled-content>‐1β), via activation of caspase‐1, which processes pro‐<jats:styled-content style="fixed-case">IL</jats:styled-content>‐1β into its mature active form. <jats:styled-content style="fixed-case">IL</jats:styled-content>‐1 has long been known to exert metabolic effects, most notably being implicated in insulin resistance and obesity. A key phenotype of the <jats:styled-content style="fixed-case">NLRP</jats:styled-content>3‐deficient mouse is insulin hypersensitivity. Over the past 5 years, a number of discoveries have been made suggesting a close interplay between <jats:styled-content style="fixed-case">NLRP</jats:styled-content>3 and metabolism. Metabolic products have been shown to activate <jats:styled-content style="fixed-case">NLPR</jats:styled-content>3, and disturbed mitochondria have been shown to be involved in <jats:styled-content style="fixed-case">NLRP</jats:styled-content>3 function. It is possible that under normal physiology <jats:styled-content style="fixed-case">NLRP</jats:styled-content>3 is homeostatic and maintains the metabolic balance. However, upon chronic activation (e.g. in obesity or hypercholesterolemia), <jats:styled-content style="fixed-case">NLRP</jats:styled-content>3 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.</jats:p>