Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of liver disorders that occurs in the context of obesity and type 2 diabetes mellitus (Chalasani et al., 2012). While pure steatosis is a largely benign condition, it can be complicated by nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver failure. The pathogenesis of NAFLD is multifactorial and triggered by environmental factors such as hypercaloric nutrition and lack of physical activity in the context of genetic predisposition (Chalasani et al., 2010; Romeo et al., 2008). Bariatric surgery is the most radical therapy for the metabolic syndrome and NASH, leading typically to massive weight loss, improvement of liver histology
(Dixon et al., 2004), and all-cause mortality (Lundell, 2012). DNA methylation represents a level of epigenetic regulation that is closely linked to transcription factor (TF) binding and chromatin accessibility. While DNA methylation been studied intensively in cancer, including hepatocellular carcinoma (Ammerpohl et al., 2012), its pathogenetic role in benign disorders is only recently being recognized. DNA methylation signatures are not static but can be remodeled by TFs (Stadler et al., 2011) and by environmental stimuli (Barre` s et al., 2012). The relevance of differential DNA methylation in NAFLD has been demonstrated for PPARGC1A, which showed a tight interaction to the insulin resistance phenotype (Sookoian et al., 2010) and by differential susceptibility of mice to hepatic steatosis (Pogribny et al., 2009) based on their epigenetic profiles. Here we present a systematic analysis of DNA methylation in NAFLD and its dynamic remodeling after the massive weight loss induced by bariatric surgery.