Hepatic SIRT6 protects against cholestatic liver disease primarily <i>via</i> inhibiting bile acid synthesis.

ABSTRACT: Cholestatic liver disease, caused by the accumulation of hazardous bile acids in the liver, may result in cirrhosis, fibrosis, or liver failure. Activation of sirtuin 6 (SIRT6) prevents cholestasis-associated pathological events, such as oxidative stress and mitochondrial biogenesis dysfunction, and inhibits bile acid synthesis to alleviate cholestatic liver injury. However, it remains uncertain which pathway mediates the therapeutic effect of SIRT6 in reducing cholestasis. Therefore, we treated liver-specific Sirt6 knockout mice with N-acetylcysteine, KEAP1-NRF2-IN-1, or acadesine to alleviate oxidative stress and/or promote mitochondrial biogenesis after modeling cholestatic liver disease, but these measures did not significantly improve cholestatic symptoms. However, MDL801, a SI

SUBMITTER: Zhang W 

PROVIDER: S-EPMC12336411 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature