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.

中文翻译：

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代谢相关性脂肪肝疾病的表观遗传学药物发现前景。

尽管进行了数十年的研究，但是缺乏用于代谢（功能障碍）相关性脂肪肝疾病（MAFLD）的有效疗法。越来越多的证据表明表观遗传失调在MAFLD中很常见，并协调了其发展和进程的许多方面。此外，响应环境线索的表观遗传修饰的高可塑性使表观遗传学成为治疗药物发现的新领域。近年来，几种基于表观遗传学的药物和诊断生物标记物已进入临床开发和/或获得监管部门的批准。在这里，我们回顾了在MAFLD期间对表观遗传调控的理解方面的最新进展，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）RNA。