Histone Methylation Regulation as a Potential Target for Non-alcoholic Fatty Liver Disease

Abstract

Epigenetic modulations are currently emerging as promising targets in metabolic diseases, including non-alcoholic fatty liver disease (NAFLD), for their roles in pathogenesis and therapeutic potential. The molecular mechanisms and modulation potential of histone methylation as a histone post-transcriptional modification in NAFLD have been recently addressed. However, a detailed overview of the histone methylation regulation in NAFLD is lacking. In this review, we comprehensively summarize the mechanisms of histone methylation regulation in NAFLD. We conducted a comprehensive database search in the PubMed database with the keywords 'histone', 'histone methylation', 'NAFLD', and 'metabolism' without time restriction. Reference lists of key documents were also reviewed to include potentially omitted articles. It has been reported that these enzymes can interact with other transcription factors or receptors under pro-NAFLD conditions, such as nutritional stress, which lead to recruitment to the promoters or transcriptional regions of key genes involved in glycolipid metabolism, ultimately regulating gene transcriptional activity to influence the expression. Histone methylation regulation has been implicated in mediating metabolic crosstalk between tissues or organs in NAFLD and serves a critical role in NAFLD development and progression. Some dietary interventions or agents targeting histone methylation have been suggested to improve NAFLD; however, there is still a lack of additional research and clinical translational relevance. In conclusion, histone methylation/demethylation has demonstrated an important regulatory role in NAFLD by mediating the expression of key glycolipid metabolism-related genes, and more research is needed in the future to explore its potential as a therapeutic target.

Keywords: Epigenetics; NAFLD; histone methylation; lipid metabolism; non-alcoholic fatty liver disease; therapy.