Commentary
In an experimental study, S. Lefere et al. investigated the efficacy of single and pan-PPAR agonists in the treatment of progressive steatohepatitis. The authors employed the CDAA-HFD (choline-deficient, amino acid-defined high-fat diet-induced) model, which induces severe inflammation and liver fibrosis. Mice were fed the CDAA-HFD for 12 weeks, and PPAR agonist treatment was administered during the last 6 weeks of diet feeding.
In this study, lanifibranor decreased serum triglyceride levels. The PPAR agonists were well tolerated, and no significant effects on body weight or adipose tissue weight were observed, while the liver-to-body weight ratio was lower in mice treated with lanifibranor.
Importantly, treatment with lanifibranor reversed steatohepatitis, as evidenced by highly significant reductions in the NAFLD activity score (NAS) as well as the subcomponent scoring of steatosis (validated by reduced hepatic triglyceride content), lobular inflammation and hepatocellular ballooning.
Lanifibranor ameliorated liver fibrosis, with significant reductions in collagen area, liver hydroxyproline, and a reduced expression of fibrogenic mediators.
