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. 2022 Feb 10;10:826204. doi: 10.3389/fcell.2022.826204

FIGURE 4.

FIGURE 4

Roles of Nrf2 in FLD. Mitochondria in NAFLD is impaired, leading to overproduction of ROS which triggers lipid peroxidation. The generated ROS and lipid peroxidation products will further damage the function of the respiratory chain, resulting in a vicious circle. ROS also activates Nrf2 to compound antioxidant proteins, alleviating NAFLD. Expression of Nrf2 is much higher in the livers of mice which fed with high-fat diet than those fed with normal chow. However, the accumulation of Nrf2 is inhibited when the intake of Met and Tyr is restricted in high-fat feeding mice. CDDO-Im, DMF, curcumin and ginkgolide B can alleviate NAFLD through activating Nrf2. Aucubin stimulates Nrf2 to compound HO-1 and SOD, alleviating NAFLD. Alcohol is metabolized to acetaldehyde in liver cells by alcohol dehydrogenase and CYP2E1. Acetaldehyde can destroy mitochondria, resulting in the production of ROS. ROS activates Nrf2 to alleviate ALD. SFN stimulates Nrf2 to compound HMOX1, NQO1 and GSTM3 for alleviating NAFLD. The up-regulation of Nrf2 was observed in knockout SNX10 mice. And SOD was compounded to alleviate ALD. ALD, alcoholic liver disease; CYP2E1, cytochrome P450 2E1; DMF, dimethyl fumarate; GSH, reduced glutathione; GSTM3, glutathione S-transferase 3; HMOX1, heme oxygenase 1; HO-1, hemeoxygenase-1; Keap1, Kelch-like ECH-associated protein 1; Met, methionine; NAFLD, non-alcoholic fatty liver disease; NQO1, quinone oxidoreductase 1; Nrf2, nuclear factor-erythroid 2-related factor 2; ROS, reactive oxygen species; SFN, sulforaphane; SNX10, sorting nexin 10; SOD, superoxide dismutase; SQSTM1, sequestosome 1; Tyr, tyrosine.