Schematic representation of the mechanism of pathogenesis of NASH from obesity-induced simple steatosis. Obesity results in insulin resistance and increased hepatic uptake of free fatty acids (FFA), which induces simple steatosis. Steatosis upregulates CYP2E1 and also generates oxidative stress. When an obese individual consumes excessive alcohol on an occasion (binge drinking), the increased CYP2E1 metabolizes ethanol into acetaldehyde through the microsomal ethanol oxidizing system, which in turn aggravates oxidative stress and produces ROS. The excess ROS along with toxic acetaldehyde causes hepatic injury and induces pathogenesis of NASH. Therefore, obesity plays as the “first hit” and a binge serves as the “second hit” toward pathogenesis of NASH in obese individuals.