The Multifaceted Role of Cytochrome P450 Isoenzymes in Alcoholic and Metabolic (Dysfunction) Fatty Liver Diseases

The current review explores the alterations in cytochrome P450 (CYP) activity and expression during alcoholic liver disease (ALD) and metabolic (dysfunction)-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD). CYP is a major family of enzymes involved in the metabolism of numerous endogenous and exogenous compounds. Thus, any change in CYP activity or expression could disrupt metabolic pathways. Alterations in hepatic CYP have been shown to contribute to the development of ALD and MAFLD, and vice versa. CYP isoforms also participate in fatty acid metabolism and are involved in fatty liver development in ALD and MAFLD by regulating various cell signaling pathways and transcription factors. Several mechanisms by which CYP causes oxidative stress and liver injury are reviewed here. Additionally, CYP isoforms are known to break down cholesterol into bile acids, which play a role in lipid absorption in the small intestine and modulate the bile acid pool. This review discusses the role of CYP isoforms in the progression of ALD and MAFLD, as understanding these mechanisms can help identify potential targets for the prevention and treatment of both diseases.