NR1H4 and Other metabolic disease: The canonical pathways associated with NAFLD and NASH analysis also indicated that FGF21 can regulate the related genes peroxisome proliferator-activated receptor gamma (PPARG), peroxisome proliferator-activated receptor alpha (PPARA), sterol regulatory element binding protein 1 (SREBF1), farnesoid X receptor (NRIH4), fatty acid synthase (FAS or FASN), and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PPARGC1A) by affecting FXR/RXR signaling to play a role in metabolic diseases (Figure 1A).