Epigenetic and epitranscriptomic regulations of metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive hepatic lipid accumulation and can progress to metabolic dysfunction-associated steatohepatitis (MASH), which is manifested with persistent liver injury, inflammation, and fibrosis, increasing the risk for cirrhosis and hepatocellular carcinoma. Aberrant epigenetic reprogramming and epitranscriptomic remodeling emerge to be a driving force for MASLD and MASH. SNAIL1 and SLUG, two related transcriptional regulators, regulate de novo lipogenesis and liver steatosis by opposing epigenetic mechanisms. RNA m6A modification regulates not only liver steatosis but also liver injury and regeneration. MASLD is associated with changes in the expression of m6A writers, erasers, and readers, which significantly influence its progression.