The Dual Role of Nrf2 in Nonalcoholic Fatty Liver Disease: Regulation of Antioxidant Defenses and Hepatic Lipid Metabolism

Figure 2

Schematic summary of the proposed protective roles of Nrf2 in nonalcoholic fatty liver disease (NAFLD). The progression from the simple accumulation of lipids in the hepatocyte to steatohepatitis (NASH) is depicted. NASH is associated with inflammation, fibrosis, and cirrhosis. The classical understanding is that Nrf2 coordinates the elimination of ROS and electrophiles derived from lipid peroxidation, thus preventing hepatocellular oxidative stress and mitochondrial dysfunction. In addition, there is growing evidence in the literature that Nrf2 regulates fatty acid metabolism by repressing genes that promote lipid accumulation in hepatocytes. In rodents, both mechanisms were shown to inhibit steatohepatitis in an age-dependent manner and can be induced via the pharmacological (e.g., CDDO-Im) or nutritional (e.g., sulforaphane) administration of Nrf2 activators.