The Epigenetic Drug Discovery Landscape for Metabolic-associated Fatty Liver Disease

Trends Genet. 2020 Jun;36(6):429-441. doi: 10.1016/j.tig.2020.03.003. Epub 2020 Mar 28.

Abstract

Despite decades of research, effective therapies for metabolic (dysfunction)-associated fatty liver disease (MAFLD) are lacking. An increasing body of evidence suggests that epigenetic dysregulation is frequent in MAFLD, and orchestrates many aspects of its development and progression. Furthermore, the high plasticity of epigenetic modifications in response to environmental cues renders epigenetics a novel area for therapeutic drug discovery. Over recent years, several epigenetics-based drugs and diagnostic biomarkers have entered clinical development and/or obtained regulatory approval. Here, we review recent advances in our understanding of epigenetic regulation and programming during MAFLD, including DNA methylation, histone modifications, chromatin remodelling, transcriptional control, and noncoding (nc)RNAs. We also discuss the potential translational implications and challenges of epigenetics in the context of MAFLD.

Keywords: DNA methylation; MAFLD; NAFLD; epigenetics; fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Discovery*
  • Epigenesis, Genetic*
  • Histones
  • Humans
  • Liver Diseases / drug therapy*
  • Liver Diseases / genetics
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / genetics
  • Protein Processing, Post-Translational*
  • RNA, Untranslated / genetics*

Substances

  • Histones
  • RNA, Untranslated