Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits. Its complexity stems from genetic predisposition, environmental influences, and metabolic factors. Epigenetic processes govern various cellular functions such as transcription, chromatin structure, and cell division. In NAFLD, these epigenetic tendencies, especially the process of histone methylation, are intricately intertwined with fat accumulation in the liver. Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis. While early-stage NAFLD is reversible, its progression to severe stages becomes almost irreversible. Therefore, early detection and intervention in NAFLD are crucial, and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.

Keywords: Non-alcoholic fatty liver disease; Mechanism; Histone methylation; Methyltransferases; Demethytrasferases; Epigenetic modification; Adipogenesis

Core Tip: Non-alcoholic fatty liver disease (NAFLD) is a global health concern accounting for a significant proportion of liver-related deaths. However, there are no Food and Drug Administration-approved drugs for NAFLD treatment. Epigenetic mechanisms play multiple roles in the pathogenesis of diseases and hold promise as potential therapeutic targets. Here, we review the impact of histone methylation on the alterations in metabolic homeostasis, inflammatory injury, fibrosis, and carcinogenesis during the progression of NAFLD, providing a theoretical foundation for target discovery and clinical treatment.