NLRP3 Inflammasome in Inflammation and Metabolism: Identifying Novel Roles in Postburn Adipose Dysfunction

Abstract

Inflammasomes are multiprotein complexes that respond to pathogen or host associated damage markers, leading to caspase-1 maturation and processing of pro-inflammatory cytokines. Initially, inflammasomes were implicated primarily in inflammatory and infectious conditions. However, increasing evidence demonstrates broader roles beyond inflammation, including regulation of adipose tissue metabolism after burns. Here, we conducted a search for articles on PubMed, Web of Science, Embase, Scopus, and UpToDate with applied search strategies including a combination of "burns," "trauma," "(NLRP3) inflammasome," "metabolic conditions," "white adipose tissue," "macrophages," "browning," and "lipolysis" and included papers from 2000 to 2020. We discuss unexpected roles for NLRP3, the most characterized inflammasome to date, as a key metabolic driver in a variety of conditions. In particular, we highlight the function of NLRP3 inflammasome in burn trauma, which is characterized by both hyperinflammation and hypermetabolism. We identify a critical part for NLRP3 activation in macrophage dynamics and delineate a novel role in postburn white adipose tissue remodeling, a pathological response associated with hypermetabolism and poor clinical outcomes. Mechanistically, how inflammation and inflammasome activation is linked to postburn hypermetabolism is a novel concept to contemplate, and herein we provide evidence of an immunometabolic crosstalk between adipocytes and infiltrating macrophages.

Keywords: NLRP3 inflammasome; browning; burns; hypermetabolism; lipolysis; macrophages.