The role of pyroptosis in metabolism and metabolic disease

Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation of membrane pores mediated by the gasdermin protein family. Two main activation pathways have been documented: the caspase-1-dependent canonical pathway and the caspase-4/5/11-dependent noncanonical pathway. Pyroptosis leads to cell swelling, lysis, and the subsequent release of inflammatory mediators, including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Chronic inflammation is a well-established foundation and driver for the development of metabolic diseases. Conversely, metabolic pathway dysregulation can also induce cellular pyroptosis. Recent studies have highlighted the significant role of pyroptosis modulation in various metabolic diseases, including type 2 diabetes mellitus, obesity, and metabolic (dysfunction) associated fatty liver disease. These findings suggest that pyroptosis may serve as a promising novel therapeutic target for metabolic diseases. This paper reviews an in-depth study of the current advancements in understanding the role of pyroptosis in the progression of metabolic diseases.