Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Trends Genet. 2020 Jun;36(6):429-441. doi: 10.1016/j.tig.2020.03.003. Epub 2020 Mar 28.
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.
尽管已经进行了几十年的研究，但代谢（功能）相关脂肪性肝病（MAFLD）的有效治疗方法仍缺乏。越来越多的证据表明，表观遗传失调在 MAFLD 中很常见，并协调其发展和进展的许多方面。此外，表观遗传修饰对环境线索的高可塑性使表观遗传学成为治疗药物发现的一个新领域。近年来，几种基于表观遗传学的药物和诊断生物标志物已进入临床开发和/或获得监管批准。在这里，我们回顾了近年来对 MAFLD 期间表观遗传调控和编程的理解的最新进展，包括 DNA 甲基化、组蛋白修饰、染色质重塑、转录控制和非编码（nc）RNAs。我们还讨论了 MAFLD 背景下表观遗传学的潜在转化意义和挑战。
