The NLRP3 Inflammasome as a Novel Player of the Intercellular Crosstalk in Metabolic Disorders

Figure 1

The release of obesity-related danger signals such as reactive oxygen species, lysosomes, and other obesity-induced danger signals resulting in the oligomerization of NLRP3 in adipose tissue. The NLRP3 inflammasome is made up of carboxy terminal leucine-rich repeats (LRRs), a nucleotide-binding domain (NBD), and an N-terminal pyrin domain (PYD). The resulting oligomerization causes the recruitment of procaspase-1 via homotypic binding of caspase activation and recruitment domain (CARD) or through the PYD by means of the adapter apoptosis-associated speck-like protein containing a CARD (ASC). Caspase-1 is therefore activated and initiates the cleavage of prointerleukin (IL)1β and pro-IL18 to form the active cytokines IL1β and IL18. The activation of caspase-1 also results in pyroptosis (a form of lytic cell death during inflammation) and the release of high mobility group box 1 (HMGB1) and IL1α.