Moderate overexpression of Sirt1 in mice protects from high-fat-diet-induced metabolic disease.48 These data are of relevance when considering epidemiological data in humans with disturbed circadian rhythms such as shift workers who have a high risk of metabolic disorders.49 However, clinical studies investigating epigenetic reprogramming in NASH are only just beginning to emerge. The gene discussed is SIRT1; the disease is metabolic disease.