NLRP3 at the interface of metabolism and inflammation

Summary The discovery of the NLRP 3 ( 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 NLRP 3‐deficient mouse is insulin hypersensitivity. Over the past 5 years, a number of discoveries have been made suggesting a close interplay between NLRP 3 and metabolism. Metabolic products have been shown to activate NLPR 3, and disturbed mitochondria have been shown to be involved in NLRP 3 function. It is possible that under normal physiology NLRP 3 is homeostatic and maintains the metabolic balance. However, upon chronic activation (e.g. in obesity or hypercholesterolemia), NLRP 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.