Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue.

ABSTRACT: In this study, we hypothesized that deregulation in the maintenance of the pool of coenzyme A (CoA) may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Specific deletion of Acot12 (Acot12^-/-), the major acyl-CoA thioesterase, induced the accumulation of acetyl-CoA and resulted in the stimulation of de novo lipogenesis (DNL) and cholesterol biosynthesis in the liver. KEGG pathway analysis suggested PPARα signaling as the most significantly enriched pathway in Acot12^-/- livers. Surprisingly, the exposure of Acot12^-/- hepatocytes to fenofibrate significantly increased the accumulation of acetyl-CoA and resulted in the stimulation of cholesterol biosynthesis and DNL. Interaction analysis, including proximity-dependent biotin

SUBMITTER: Park S 

PROVIDER: S-EPMC8333268 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature