Regulatory Role of Nuclear Factor of Activated T Cells c4 in the Development of Metabolic dysfunction-associated Fatty Liver Disease.

purpose of reviewThis review aims to summarize the current understanding of the regulatory mechanisms of nuclear factor of activated T cells c4 (NFATc4) in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). We focus on the multifaceted roles of NFATc4 in lipid metabolism, oxidative stress, inflammation, and insulin resistance, with the goal of evaluating its potential as a therapeutic target for MAFLD. RECENT

findingsEmerging evidence indicates that NFATc4 is significantly upregulated in MAFLD patients and animal models. It promotes hepatic steatosis by inhibiting PPARα-mediated fatty acid oxidation, enhances oxidative stress via mitochondrial dysfunction, exacerbates inflammation through cytokine regulation and immune cell activation, and contributes to insulin resistance by modulating adipokine expression. Pharmacological inhibition of NFATc4 has shown protective effects in preclinical models, highlighting its therapeutic potential. NFATc4 serves as a critical transcriptional regulator in the progression of MAFLD, influencing multiple pathological processes through its nuclear translocation and interaction with key metabolic and inflammatory pathways. Targeting NFATc4 may offer a promising strategy for the treatment of MAFLD, though further research is needed to elucidate cell-type-specific mechanisms and develop tissue-specific inhibitors.