EZH2 as a potential target for NAFLD therapy

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a complex disease that is affected by genetic predisposition and epigenetic modification. Deregulation of epigenetic pathways is now recognized as a frequent event in NAFLD, and understanding the mechanistic roles of these epigenetic factors may lead to new strategies for NAFLD treatment. Enhancer of zeste homolog 2 (EZH2) catalyzes methylation on Lys 27 of histone H3, which leads to chromatin compaction and gene silencing. EZH2 regulates embryonic development and cell lineage determination and is related to many human diseases. Recent studies show that EZH2 has critical roles in liver development, homeostasis, and regeneration. Moreover, aberrant activation of EZH2 promotes NAFLD progression. Several EZH2 inhibitors have been developed and studied both in vitro and in clinical trials. In this review, we summarize our current understanding of the role of EZH2 in NAFLD and highlight its potential as a novel therapeutic target for NAFLD treatment.