Role of PPARα in alcohol metabolism. Ethanol is metabolized by ADH, CYP2E1, and CAT to produce acetaldehyde. Toxic acetaldehyde and CYP2E1-generated ROS can induce hepatocellular injury by inactivating PPARα. PPARα activation enhances detoxification of FFA-derived lipotoxicity by modulating the expression of most key genes involved in FA catabolism and suppresses ROS production by switching alcohol metabolism from the CYP2E1 pathway to the CAT pathway, which restores the balance between oxidants and antioxidants, FA oxidation and synthesis, and thus prevents alcohol-arisen liver injury. Abbreviations: ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; CAT, catalase; CYP2E1, cytochrome P450 2E1; FA, fatty acid; FFA, free fatty acid; PPARα, peroxisome proliferator-activated receptor alpha; ROS, reactive oxygen species; RXRα, retinoid X receptor.