MLN4924 Treatment Diminishes Excessive Lipid Storage in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Stimulating Hepatic Mitochondrial Fatty Acid Oxidation and Lipid Metabolites.

ABSTRACT: MLN4924 is a selective neddylation inhibitor that has shown great potential in treating several cancer and metabolic diseases, including obesity. However, it remains largely unknown whether MLN4924 has similar effect on non-alcoholic liver disease (NAFLD), which is closely associated with metabolic disorders. Here, we investigated the role of MLN4924 in NAFLD treatment and the underlying mechanism of the action using primary hepatocytes stimulated with free fatty acid, as well as high-fat diet (HFD)-induced NAFLD mouse models. We found that MLN4924 can inhibit the accumulation of lipid and reduce the expression of peroxisome proliferator-activated receptor γ (PPARγ), a key player in adipocyte differentiation and function in both in vivo and in vitro models. Moreover, we verified its import

SUBMITTER: Ge M 

PROVIDER: S-EPMC9696831 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature