We aimed to elucidate the underlying mechanisms of FGF21-mediated hepatoprotective effects on NASH, by using APOE*3-Leiden.CETP mice fed with an HFCD, a model that induces all stages of NASH in a human-like fashion and recapitulates the ultrastructural changes observed in NASH patients (Morrison et al., 2015; Liang et al., 2014). This evidence concerns the gene FGF21 and metabolic dysfunction-associated steatohepatitis.