Deciphering the role of aberrant DNA methylation in NAFLD and NASH

The global incidence of nonalcoholic fatty liver disease (NAFLD) is mounting incessantly, and it is emerging as the most frequent cause of chronic and end stage liver disorders. It is the starting point for a range of conditions from simple steatosis to more progressive nonalcoholic steatohepatitis (NASH) and associated hepatocellular carcinoma (HCC). Dysregulation of insulin secretion and dyslipidemia due to obesity and other lifestyle variables are the primary contributors to establishment of NAFLD. Onset and progression of NAFLD is orchestrated by an interplay of metabolic environment with genetic and epigenetic factors. An incompletely understood mechanism of NAFLD progression has greatly hampered the progress in identification of novel prognostic and therapeutic strategies. Emerging evidence suggests altered DNA methylation pattern as a key determinant of NAFLD pathogenesis. Environmental and lifestyle factors can manipulate DNA methylation patterns in a reversible manner, which manifests as changes in gene expression. In this review we attempt to highlight the importance of DNA methylation in establishment and progression of NAFLD. Development of novel diagnostic, prognostic and therapeutic strategies centered around DNA methylation signatures and modifiers has also been explored.