Farnesoid X Receptor Agonist INT-787 Inhibits Hepatic Mitochondrial Dysfunction in a Diet-Induced ob/ob Mouse Model of MASH.

ABSTRACT: This study evaluated the protective role of farnesoid-X-receptor (FXR) agonist INT-787 in the control of mitochondrial changes using a metabolic dysfunction-associated steatohepatitis (MASH) model. Lep-ob/ob mice were fed a control diet (CD) for 21 weeks (wks), or a high-fat diet (HFD) for 9 or 21 wks; in the 21 wk HFD groups, INT-787 (30 mg/kg/day) dosed via HFD admixture was added. The hepatic ATP, ROS, GSH and MIC19, which stabilizes the structure of inner mitochondrial membrane (IMM), were quantified. Transmission electron microscopy (TEM) analysis was also performed. INT-787 increased hepatic ATP, which was downregulated after HFD 9 and 21 wks. Hepatic ROS increased and GSH decreased after 21 wks and were recovered by INT-787. MIC19 mRNA level decreased after HFD 21 wks, and it was co

SUBMITTER: Di Pasqua LG 

PROVIDER: S-EPMC12652301 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature