The Role of NLRP3 Inflammasome in the Pathogenesis and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease characterized by excessive hepatic lipid accumulation and closely associated with metabolic disorders. Its progression involves not only abnormal lipid metabolism but also inflammatory responses, oxidative stress, mitochondrial dysfunction, and fibrosis formation. The NLRP3 inflammasome, as an important component of innate immunity, plays a key role in regulating inflammation under metabolic stress conditions. When activated by factors such as lipid overload, reactive oxygen species production, mitochondrial damage, and gut-derived inflammatory signals, the NLRP3 inflammasome promotes the activation of Caspase-1 and the release of inflammatory cytokines, including interleukin-1β and interleukin-18. These inflammatory responses affect hepatocytes, Kupffer cells, and hepatic stellate cells, contributing to liver inflammation and fibrosis during MASLD progression. This paper discusses the biological characteristics and activation mechanisms of the NLRP3 inflammasome and analyzes its involvement in hepatic lipid accumulation, chronic inflammation, metabolic disorders, and fibrosis development. The interaction between NLRP3 signaling and oxidative stress, insulin resistance, and the gut-liver axis is also examined. Targeting the NLRP3 inflammasome may provide a potential approach for MASLD management, although further studies are needed to clarify its clinical application and safety.