(A and B) Hepatic Fgf21 mRNA (A) and plasma FGF21 protein (B) levels in 11- to 13-week-old male WT C57Bl/6 mice ad libitum fed chow and provided water, 0.2% saccharin (sacc), 10% glucose (gluc), 10% fructose (fruc), or 10% sucrose (sucr) ad libitum in a drinking bottle for 24 hr (n = 5/group).

(C and D) Hepatic Fgf21 mRNA (C) and plasma FGF21 protein (D) levels in 11- to 13-week-old male WT C57Bl/6 mice ad libitum fed chow and provided 10% sucrose ad libitum for the indicated time (n = 5/group).

(E and F) Hepatic Fgf21 mRNA (E) and plasma FGF21 protein (F) levels in 10- to 12-week-old male WT (FGF21fl/fl) and FGF21 liver-specific knockout (FGF21 LivKO) mice ad libitum fed chow and 10% sucrose ad libitum for 24 hr (n = 5–7/group).

(G) HSD preference ratio in 10- to 12-week-old male WT and FGF21 LivKO mice (n = 5/group).

(H) Plasma FGF21 levels in human subjects maintained at hyperglycemia via dextrose infusion for 0, 2, and 24 hr (n = 10).

(I) Plasma FGF21 levels in WT and ChREBP KO mice ad libitum fed chow and 10% sucrose ad libitum for 24 hr (n = 5–8/group). Values are represented as mean ± SEM (∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.005; ∗∗∗, #p < 0.001 compared to WT).