Transcriptomic Profiling Reveals Inflammatory, Fibrotic, and Apoptotic Signatures in a Methionine-Choline-Deficient Diet-Induced Murine Model of Metabolism-Dysfunction-Associated Steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH; formerly non-alcoholic steatohepatitis, NASH) is characterized by oxidative stress, inflammatory activation, hepatocellular injury, and progressive liver dysfunction. However, the global transcriptomic landscape underlying stress-induced hepatic injury remains incompletely understood. In this study, we employed a methionine-choline-deficient (MCD) diet-induced murine model to characterize the phenotypic and transcriptomic alterations associated with liver injury. Male C57BL/6J mice were fed either a control or MCD diet, and hepatotoxicity was assessed by survival analysis, body and liver weight measurements, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, histopathological examination, RNA sequencing, quantitative real-time PCR (qRT-PCR), and tumor necrosis factor-alpha (TNF-α) enzyme-linked immunosorbent assay (ELISA). MCD feeding markedly reduced survival and body weight while inducing hepatomegaly and significant elevations in serum ALT and AST, indicating severe hepatocellular injury. Histopathological analysis demonstrated hepatic steatosis, hepatocellular ballooning, and lobular inflammation without histological evidence of fibrosis. Transcriptomic profiling revealed extensive gene expression remodeling, characterized by activation of inflammatory pathways, enrichment of MAPK-related signaling, dysregulation of lipid metabolism, suppression of antioxidant defense systems, impairment of cytochrome P450-mediated detoxification, and upregulation of apoptosis-associated genes. qRT-PCR further validated the differential expression of representative genes involved in inflammatory signaling (