Identification of cytochrome CYP2E1 as critical mediator of alcohol effects on steatotic hepatocytes

Background & Aims: Several clinical studies proposed a strong causative link between the consumption of alcohol and progressive liver disease in obese individuals. However, it is incompletely understood how alcohol and obesity interact and whether the combined pathological effects are additive or synergistic. Here, we aimed to establish an in vitro model for joint effects of alcohol and steatosis in hepatocytes. Methods and Results: Lipid accumulation in primary human hepatocytes was induced by incubation with the fatty acid oleate. Subsequently, steatotic and control hepatocytes were incubated with up to 50 mM…