Fig. 4: FGF21 is required for the protective effects of carbohydrate loading.

a Serum FGF21 levels after one week of preconditioning with standard (Ctrl) or 50% sucrose-water (HC). b Food (left) and water (right) intake (normalized by body weight) after one week of preconditioning with the indicated diet. c Serum urea (AUC) and (d) serum creatinine levels at day 2 post-renal IRI after one week of preconditioning with the indicated diet. e Representative cross sections of PAS-stained kidneys (left; x10 magnification; scale bar 100 µm) and histological score (right) at day 2 post-renal IRI after one week of preconditioning with the indicated diet. f Representative cross sections of PAS-stained kidneys with necrotic area digitally highlighted in red (left; x10 magnification; scale bar 100 µm) and quantification of necrotic tissue area (right) at day 2 post-renal IRI after one week of preconditioning with the indicated diet. g Relative Krt20 mRNA levels in the kidney at day 2 post-renal IRI after one week of preconditioning with the indicated diet. h Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme levels at the indicated time post-hepatic IRI. i Representative cross sections of H&E-stained livers (x20 magnification; scale bar 30 µm) at day 1 post-hepatic IRI. Ischemic areas appearing in light pink. j Relative Hmgb1 mRNA levels in the liver at day 2 post-renal IRI after one week of preconditioning with the indicated diet. *p values for a,c-g,j were calculated with two-way ANOVA followed by a Tukey’s post hoc analysis, b with two-way RM ANOVA with Geisser-Greenhouse correction and h with two-way ANOVA followed by a Sidak’s post hoc analysis, *p < 0.05 **p < 0.01 ***p < 0.001 ****p < 0.0001 a p < 0.05 aaaa p < 0.0001 Fgf21^WT HC vs. Fgf21^WT Ctrl, bbbb p < 0.0001 Fgf21^KO HC vs. Fgf21^WT Ctrl. p values for a < 0.0001, <0.0001 and <0.0001, for b < 0.0001 and <0.0001, for c = 0.0269 and 0.0008, for d = 0.0453, for e = 0.0236 and 0.001, for f < 0.0001, <0.0001 and = 0.0074, for g = 0.0002 and 0.0031, for h = 0.0328 and 0.0351, for j = 0.007 and 0.022. In a-j, experiments were carried out in Fgf21^WT and Fgf21^KO10-weeks old male mice. Sample sizes: (a–g), n = 10–15, n = 15 for Fgf21^WT Ctrl, n = 15 for Fgf21^WT HC, n = 15 Fgf21^KO Ctrl, n = 10 for Fgf21^KO HC; (h–j), n = 6–13, n = 6 Fgf21^WT Ctrl and HC, n = 10 for Fgf21^KO Ctrl, n = 13 for Fgf21^KO HC. Data in all panels are shown as mean ± SD. See also Supplementary Data Fig. 6.