Classical NLRP3-inflammasome activation mediated maturation of pro-inflammatory signals in adipose tissue. (a): Individual components of NLRP3 inflammasome. It consists of NLRP3 protein with leucine-rich repeats (LRR), globular NACHT domain, and homologous PYD domain, which interact with PYD of adapter ASC. The CARD domain of ASC allows interaction with pro-caspase-1, which matures into caspase-1 upon NLRP3 inflammasome activation and oligomerization. (b): NLRP3 inflammasome activation in adipocyte invading ATM’s requires two signals. The first signal involves the priming signal, which is induced by endogenous cytokines or microbial components, such as lipopolysaccharide (LPS), leading to NF-κB-mediated upregulation of NLRP3 and pro-IL-1β. The second signal triggered by specific stimuli, PAMPs, and DAMPs, results in stresses, such as K+ efflux, mitochondrial dysfunction, and lysosomal disruption, which stimulates NLRP3 inflammasome formation. The activation of the NLRP3 inflammasome leads to procaspase-1 self-cleavage, generating active caspase-1, which in turn mediates IL-1β and IL-18 secretion and pyroptosis.