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

Abstract

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.

Keywords

SNAIL1 / SLUG / m⁶A / MASLD / MASH

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