Lack of hepatic keap-1 ameliorates steatosis through a negative LXR modulation without altering the innate immune response in a diet-induced model of nonalcoholic steato-hepatitis

Background: Although the generation of reactive oxygen species (ROS) in response to triglyceride accumulation has been classically proposed as a possible “second hit” enabling the progression from simple steatosis to NASH, so far, functional studies failed to demonstrate an indispensable role for oxidative stress in this process. Methods: Hepatocyte-specific keap-1 knockout mice (Keap1Δhepa), over expressing the antioxidant regulator Nrf2, were generated and fed a Methionine-Choline-Deficient (MCD) diet for 4 weeks in order to investigate the influence of Nrf2 activation on hepatic lipid metabolism, liver injury…