Complete inhibition of liver acetyl-CoA carboxylase activity is required to exacerbate liver tumorigenesis in mice treated with diethylnitrosamine.

ABSTRACT:

Background

The metabolic pathway of de novo lipogenesis (DNL) is upregulated in fatty liver disease and liver cancer. Inhibitors of DNL are in development for the treatment of these disorders; however, our previous study showed that blocking DNL unexpectedly exacerbated liver tumorigenesis when liver acetyl-CoA carboxylase (ACC) 1 and 2 enzymes were deleted in mice treated with diethylnitrosamine (DEN) and fed high fat diet. Herein, we used 3 new approaches including ACC1 vs. ACC2 isotype-selective inhibition, delaying ACC inhibition until after carcinogen treatment, and feeding mice normal chow diet to better understand the impact of ACC inhibition on liver tumorigenesis.

Methods

Six genotypes of female C57BL/6J mice with floxed ACC1 and/or ACC2 alleles were injected with D

SUBMITTER: Shrestha R 

PROVIDER: S-EPMC11559202 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature