Oxidative stress triggers lipid droplet accumulation in primary cultured hepatocytes by activating fatty acid synthesis

Despite the impaired intestinal lipid absorption and low level of visceral fat, the Sod1-deficient mouse is susceptible to developing liver steatosis. To gain insights into the mechanism responsible for this abnormal lipid metabolism, we analyzed primary cultured hepatocytes obtained from Sod1-deficient and wild-type mice. Lipid droplets began to accumulate in the cultured hepatocytes and was further increased by a Sod1 deficiency. Levels of enzymes involved in lipogenesis were elevated. It thus appears that lipogenesis is activated by oxidative stress, which is more prominent in the case of Sod1 deficiency, and appears to participate in liver steatosis. ROS cause ER stress, which consequently results in the accumulation of lipid droplets in hepatocytes by stimulating lipid synthesis via activation of SREBP1. [Display omitted] •The accumulation of lipid droplets proceeds in primary cultured hepatocytes.•The lipid droplet accumulation is enhanced in the case of a Sod1-deficiency.•Fatty acid synthesis controlled by SREBP1 is activated in this situation.•Oxidative stress appears to be involved in this accumulation of lipid droplets.