(a) WT, saline-treated FGF21-KO, and FGF21-treated FGF21-KO mice (FGF21 rx) showed no significant differences in body weight after 4 weeks on the MCD diet nor when treated to WT mice. (b) Representative liver sections showing that the severe hepatic steatosis in the saline-treated FGF21-KO mice is significantly improved with FGF21 treatment, as assessed by hematoxylin and eosin staining (10x and 20x magnification). Sirius red staining demonstrates improvement in perisinusoidal fibrosis in the FGF21-treated mice. A significant improvement is also observed in WT treated mice. (c) While the KO mice had heavier livers and a higher liver to body weight ratio than WT mice, FGF21-treated mice showed a significant decrease in liver to body weight ratio. This was also seen in WT treated mice. (d) Hepatic triglycerides are reduced to WT levels in FGF21-treated KO mice and are further reduced in treated WT animals. (e) Hepatic malondialdehyde levels are decreased to near that of WT levels in FGF21-treated mice. (f) Dramatic reductions in ALT are observed in mice treated with FGF21 for 10 days. Data are shown as mean ± SEM, N = 5 per group. ((WT v FGF21KO; *, P < 0.05; **, P < 0.01; *** P< 0.001) (FGF21KO v FGF21rx; #, P<0.05)).