Epigenetics in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC). NAFLD shares, in part, the common pathogenesis of metabolic syndrome including obesity, hyperlipidemia, insulin resistance, mitochondrial damage, oxidative stress response, and the release of inflammatory cytokines. Epigenetics, an inheritable phenomenon that affects gene expression without altering the DNA sequence, provides a new perspective on the pathogenesis of NAFLD. Reversible epigenetic changes take place at the transcriptional level and provide a phenotypic connection between the host and environment. An accumulating body of evidence suggests the importance of epigenetic roles in NAFLD, which in turn can be identified as potential therapeutic targets and non-invasive biomarkers of NAFLD. It is anticipated that the epigenetic modifiers in NAFLD may provide novel molecular indicators that can determine not only the initial risk but also the disease progression and prognosis. In the present review, we update the roles of epigenetics as pathologic mechanisms, therapeutic targets and biomarkers in NAFLD.