Figure 2.

The mechanism of ROS-mediated oxidative stress and lipid metabolism in hepatocytes. In the NAFLD patients, the overload intake of free fatty acids increases fatty acid β-oxidation and electron transport chain activity in the mitochondria. This ultimately leads to an increased release of ROS as byproduct of metabolism. The lots of ROS can directly target mitochondria, resulting in decreased energy metabolism, increased release of mtDNA and mitochondrial dysfunction. At the same time, mtROS leads to disturbance of mitochondrial membrane potential. High mitochondrial membrane potential is not friendly to the occurrence of mitophagy. The reduction of mitophagy reduces the clearance of damaged mitochondria and indirectly increases the fat synthesis. Moreover, high levels of ROS activate AMPK, SREBP1, NF-kB, JNK/cJun, and downregulate NRF2. These protein kinases and transcription factors regulate lipid metabolism, inflammation, antioxidant capacity and hepatocytes apoptosis. Finally, with the increase in insulin resistance, the synthesis of fat is intensified in hepatocytes.