Discovery of a selective cytochrome P450 4A inhibitor for the treatment of metabolic dysfunction-associated fatty liver disease

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD), a revised definition of nonalcoholic fatty liver disease (NAFLD), comprises patients with hepatic steatosis who fulfil the criteria of overweight/obesity, type II diabetes mellitus (T2DM), or more than two metabolic abnormalities, providing a valuable tool for identifying patients with fatty liver at higher risk of disease progression. we suggest that CYP4A holds significant promise for the treatment of MAFLD, and the discovery of a CYP4A inhibitor may serve as a potent drug candidate. In conclusion, our findings highlight the promising therapeutic potential of CYP4A inhibitors in addressing MAFLD. These inhibitors operate through three distinct mechanisms: ER stress/oxidative stress, Fatty acid translocase (FAT/CD36)/lipotoxicity, and inflammation/fibrosis (Figure 4G). Our results demonstrate that these inhibitors could serve as innovative candidates, introducing a novel concept in the medical field for the treatment of MAFLD.