A. An adenovirus vector encoding FGF21 (Ad-FGF21) is overexpressed in HEK293A cells. B. Adenoviral overexpression of FGF21 in SIRT1 LKO mice (n = 4-7) is evidenced by increased hepatic gene expression, protein production, and circulating levels of FGF21. C and D. Fasting-induced hepatic steatosis in SIRT1 LKO mice is ameliorated by hepatic overexpression of FGF21, as indicated by decreased Oil Red O stained areas and lowered hepatic triglyceride levels. E and F. Suppression of hepatic fatty acid oxidation and ketogenesis in SIRT1 LKO mice is prevented by hepatic overexpression of FGF21. *P<0.05, vs Ad-GFP-injected WT mice; #P<0.05, vs Ad-GFP-injected SIRT1 LKO mice.