NSC48160 targets AMPKα to ameliorate nonalcoholic steatohepatitis by inhibiting lipogenesis and mitochondrial oxidative stress.

ABSTRACT: Hepatic steatosis, which is triggered by dysregulation of lipid metabolism and redox equilibrium in the liver, is regarded as a risk factor in the non-alcoholic fatty liver disease (NAFLD). However, pharmacologic engagement of this process is difficult. We identified the small molecule NSC48160 as an effective agent against nonalcoholic steatohepatitis (NASH). We found that NSC48160 significantly lowered hepatic lipid levels in vitro and in vivo by activating the AMPKα-dependent pathway. AMPKα regulated its downstream pathway involved in lipogenesis (SREBP-1c/FASN pathway) and fatty acid oxidation (PPARα pathway). Metabonomics analysis combined with RNA-sequencing profiling revealed that NSC48160-induced lipogenesis is modulated by lipid metabolism. Moreover, NSC48160 dramati

SUBMITTER: Zhang J 

PROVIDER: S-EPMC10753068 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature