NUAK1 promotes metabolic dysfunction-associated steatohepatitis progression by activating Caspase 6-driven pyroptosis and inflammation.

ABSTRACT:

Background

lNUAK1 is strongly associated with organ fibrosis, but its causal mechanism for modulating lipid metabolism and hepatic inflammation underlying MASH has not been fully clarified.

Method

In our study, human liver tissues from patients with MASH and control subjects were obtained to evaluate NUAK1 expression. MASH models were established using C57BL/6 mice. Liver damage and molecular mechanisms of the NUAK1-Caspase 6 signaling were tested in vivo and in vitro.

Results

In the clinical arm, NUAK1 expression was upregulated in liver samples from patients with MASH. Moreover, increased NUAK1 was detected in mouse MASH models. NUAK1 inhibition ameliorated steatohepatitis development in MASH mice accompanied by the downregulation of hepatic steatosis and fibrosis.

SUBMITTER: Sheng M 

PROVIDER: S-EPMC11227355 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature