Hepatocellular cystathionine γ lyase/hydrogen sulfide attenuates nonalcoholic fatty liver disease by activating farnesoid X receptor.

ABSTRACT:

Background and aims

Hydrogen sulfide (H₂ S) plays a protective role in NAFLD. However, whether cystathionine γ lyase (CSE), a dominant H₂ S generating enzyme in hepatocytes, has a role in the pathogenesis of NAFLD is currently unclear.

Approach and results

We showed that CSE protein expression is dramatically downregulated, especially in fibrotic areas, in livers from patients with NAFLD. In high-fat diet (HFD)-induced NAFLD mice or an oleic acid-induced hepatocyte model, the CSE/H₂ S pathway is also downregulated. To illustrate a regulatory role for CSE in NAFLD, we generated a hepatocyte-specific CSE knockout mouse (CSE^LKO ). Feeding an HFD to CSE^LKO mice, they showed more hepatic lipid deposition with increased activi

SUBMITTER: Xu W 

PROVIDER: S-EPMC9795901 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature