Figure 2. Liver-derived FGF21 is required for ketogenic diet-induced drinking.

(A) Daily water intake (ml/g·BW) in wild type (WT) and FGF21-knockout (F21 KO) mice fed either a normal chow diet (NCD) or ketogenic diet (KD) (n = 8/group). The study was repeated independently three times with similar results. Values are means ± SEM. **p < 0.01 for WT NCD vs. WT KD groups; ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 for WT + KD vs. KO + KD by two-way ANOVA with Tukey's post hoc test.

(B) Daily water intake in groups of WT and hepatocyte-specific FGF21-KO (Fgf21^Alb) mice fed either a NCD (days 1 and 2) or a KD (days 3–19) (n = 6/group). Values are means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 for Fgf21^fl/fl NCD (on days 1 and 2) vs. Fgf21^fl/fl KD groups; ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 for Fgf21^fl/fl vs. Fgf21^alb by two-way ANOVA with Tukey's post hoc test.

(C) Total body water (left panel) and hydration ratios (right panel) were measured using an Echo MRI in WT and FGF21-KO mice after 3 weeks on either a NCD or KD (n = 7–8/group). Values are means ± SEM. **p < 0.01, for NCD vs. KD groups with the same genotype; ^#p < 0.05, for WT + KD vs. KO + KD by two-way ANOVA with Tukey's post hoc test.

(D) Plasma osmolality in wild type (WT) and FGF21-knockout (KO) mice fed either a normal chow diet (NCD, n = 6/group) or ketogenic diet (KD, n = 7/group). Values are means ± SEM.

(E) Systolic and diastolic blood pressure measurements in groups of WT and FGF21-KO mice fed either NCD or KD (n = 8/group). Measurements were done using a tail-cuff device over a 7 day period. Values are means ± SEM. *p < 0.05, **p < 0.01 for WT vs. FGF21-KO groups by Student’s t-test.

(F, G) Hepatic Fgf21 mRNA (F) and plasma FGF21 concentrations (G) in WT and FGF21-KO mice fed a NCD or KD. In (F), the Fgf21 QPCR Ct value for the WT/KD group is shown. Values are means ± SEM. **p < 0.01, ***p < 0.001 for NCD vs. KD groups by Student’s t-test. N.D., not detected.

See also Figure S2.