Fig. 5
Physiological dose of rmFGF21 restores insulin sensitivity in FGF21KO mice. a–c GTT (a), AUC analysis of GTT (b) and ITT performed in WT+Vehicle (c), FGF21KO + Vehicle and FGF21KO+rmFGF21 groups after 4 weeks of intervention. n = 6. These results were reproduced in four independent experiments. *comparison of WT + Vehicle vs. FGF21KO + Vehicle, #comparison of FGF21KO + Vehicle vs. FGF21KO + rmFGF21. d Whole-body insulin sensitivity as quantified by GIR. n = 6. These results of hyperinsulinemic–euglycemic clamp were reproduced in two independent experiments. e HGP in the basal and clamp state. f–j Insulin-stimulated 2-[14C]DG uptake in inguinal SAT (f, g), epiVAT (h), muscle (i) and BAT among three groups after 4 weeks of intervention (j). k Immunoblot of in vivo insulin-stimulated SAT after replenishment with rmFGF21 to HFD-induced level in FGF21KO mice. Representative immunoblots showing phospho (S473) and total Akt in the SAT of three groups. The tissues were collected at 10 min after single i.v. injection of insulin (1 U kg−1) in mice. n = 6. The bar chart shows the densitometric analysis of phosphorylation levels. l, m Change of serum adiponectin (l) and adiponectin expression in different fat depots (SAT and VAT) among WT+Vehicle, FGF21KO+Vehicle and FGF21KO +rmFGF21 groups after 4 weeks of intervention were measured by ELISA and RT-qPCR (m). n = 6. These results were reproduced in four independent experiments. Data are presented as mean ± s.e.m. Significance was determined by one-way ANOVA (b,d–m) and two-way ANOVA with Bonferroni multiple-comparison analysis (a, c). * or # P < 0.05, ** or ## P < 0.01, ***P < 0.001, NS non-significance
