The role of hepatocyte epigenetics in the pathogenesis of metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, and it can progress to cirrhosis and hepatocellular carcinoma (HCC). Genetic susceptibility, the gut microbiota, changes in hepatic metabolic pathways, the regulation of lipid metabolism pathways, cellular interactions in the liver, and epigenetic modifications all significantly contribute to MASLD pathogenesis. Recently, epigenetic changes involved in the development and occurrence of MASLD have garnered increasing attention. However, current epigenetic research predominantly focuses on the serum or liver at the whole-tissue level. Consequently, the epigenetic regulation within specific liver cell types, particularly hepatocytes, remains unclear, and its precise mechanisms are not fully understood. This article discusses in detail the specific epigenetic regulatory mechanism of hepatocytes during the occurrence of MASLD, as well as possible therapeutic targets and therapies for these modifications. Zhu et al. review the diverse epigenetic regulatory mechanisms within hepatocytes that contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). They highlight how these cell-type-specific epigenetic changes drive disease progression and discuss their emerging potential as diagnostic biomarkers and therapeutic targets.