Sun Chao, Fan Jian-Gao, Qiao Liang
Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Storr Liver Centre, Westmead Millennium Institute for Medical Research, University of Sydney, the Westmead Clinical School, Westmead Hospital, Westmead, NSW 2145, Australia.
Int J Mol Sci. 2015 Mar 5;16(3):5161-79. doi: 10.3390/ijms16035161.
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the liver. It ranges from simple steatosis to its more aggressive form, non-alcoholic steatohepatitis (NASH), which may develop into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC) if it persists for a long time. However, the exact pathogenesis of NAFLD and the related metabolic disorders remain unclear. Epigenetic changes are stable alterations that take place at the transcriptional level without altering the underlying DNA sequence. DNA methylation, histone modifications and microRNA are among the most common forms of epigenetic modification. Epigenetic alterations are involved in the regulation of hepatic lipid metabolism, insulin resistance, mitochondrial damage, oxidative stress response, and the release of inflammatory cytokines, all of which have been implicated in the development and progression of NAFLD. This review summarizes the current advances in the potential epigenetic mechanism of NAFLD. Elucidation of epigenetic factors may facilitate the identification of early diagnositic biomarkers and development of therapeutic strategies for NAFLD.
非酒精性脂肪性肝病（NAFLD）的特征是肝脏中脂肪过度积累。它的范围从单纯性脂肪变性到更具侵袭性的形式，即非酒精性脂肪性肝炎（NASH），如果长期持续，NASH可能发展为肝纤维化、肝硬化或肝细胞癌（HCC）。然而，NAFLD的确切发病机制以及相关的代谢紊乱仍不清楚。表观遗传变化是在转录水平发生的稳定改变，而不改变潜在的DNA序列。DNA甲基化、组蛋白修饰和微小RNA是最常见的表观遗传修饰形式。表观遗传改变参与肝脏脂质代谢、胰岛素抵抗、线粒体损伤、氧化应激反应以及炎症细胞因子释放的调节，所有这些都与NAFLD的发生和发展有关。本综述总结了NAFLD潜在表观遗传机制的当前进展。阐明表观遗传因素可能有助于识别早期诊断生物标志物并制定NAFLD的治疗策略。
