NR1H4 and Other metabolic disease: A recent study suggested that mouse FGF15 and human FGF19 exhibited different biological activities in mice; unlike FGF19, FGF15 lacked the protective effects on diabetes remission and did not induce HCC development in the mouse models with metabolic disorders (i.e., db/db, diet-induced obese, and MDR2 KO mice), while both FGF15 and FGF19 suppressed BA synthesis, raising the concern of depending on rodent models for the safety assessment of FXR activators [161].