Targeting glutamine metabolism in hepatic stellate cells alleviates liver fibrosis.

ABSTRACT: Glutamine metabolism plays an essential role in cell growth, and glutamate dehydrogenase (GDH) is a key enzyme. GDH promotes the metabolism of glutamate and glutamine to generate ATP, which is profoundly increased in multiple human cancers. Through in vitro and in vivo experiments, we verified that the small-molecule GDH inhibitor EGCG slowed the progression of fibrosis by inhibiting GDH enzyme activity and glutamine metabolism. SIRT4 is a mitochondrial enzyme with NAD that promotes ADP ribosylation and downregulates GDH activity. The role of SIRT4 in liver fibrosis and the related mechanisms are unknown. In this study, we measured the expression of SIRT4 and found that it was downregulated in liver fibrosis. Modest overexpression of SIRT4 protected the liver from fibrosis by inhibiting th

SUBMITTER: Yin X 

PROVIDER: S-EPMC9663710 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature