Deletion of hepatic small heterodimer partner ameliorates development of nonalcoholic steatohepatitis in mice.

ABSTRACT: Small heterodimer partner (SHP, Nr0b2) is an orphan nuclear receptor that regulates bile acid, lipid, and glucose metabolism. Shp^-/- mice are resistant to diet-induced obesity and hepatic steatosis. In this study, we explored the potential role of SHP in the development of nonalcoholic steatohepatitis (NASH). A 6-month Western diet (WD) regimen was used to induce NASH. Shp deletion protected mice from NASH progression by inhibiting inflammatory and fibrotic genes, oxidative stress, and macrophage infiltration. WD feeding disrupted the ultrastructure of hepatic mitochondria in WT mice but not in Shp^-/- mice. In ApoE^-/- mice, Shp deletion also effectively ameliorated hepatic inflammation after a 1 week WD regimen without an apparent antisteatotic effect. More

SUBMITTER: Lee YK 

PROVIDER: S-EPMC10665942 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature