Fig. 6: Hepatic FGF21 is required to fully achieve BAT activation by G49. | Nature Communications

Fig. 6: Hepatic FGF21 is required to fully achieve BAT activation by G49.

From: The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk

Fig. 6: Hepatic FGF21 is required to fully achieve BAT activation by G49.The alternative text for this image may have been generated using AI.

A BW evolution (AlbCre n = 6, AlbCre + G49 n = 10; FGF21Alb-KO n = 4, FGF21Alb-KO + G49 n = 6). Two-way RM ANOVA with Bonferroni post hoc test. p values detailed in Source data file. Cumulative food intake (n = 4 except in FGF21Alb-KO n = 3). AlbCre vs. FGF21Alb-KO: $$$p < 0.0001; AlbCre + G49 vs. FGF21Alb-KO + G49, $$$p < 0.0001. Cumulative food intake evolution. Two-way RM ANOVA with Bonferroni post hoc test. p values detailed in Source data file. B Plasma FFAs (AlbCre n = 6, AlbCre + G49 n = 6; FGF21Alb-KO n = 7, FGF21Alb-KO + G49 n = 7). 0 vs. 6 h: AlbCre, ***p = 0.0002; FGF21Alb-KO, ***p < 0.0001. C Plasma insulin (n = 6 except AlbCre + G49 t0, n = 5). 0 vs. 6 h: AlbCre, ***p < 0.0001; FGF21Alb-KO, ***p < 0.0001; AlbCre vs. FGF21Alb-KO: 6 h, ###p < 0.0001. D Blood ketone bodies (n = 6 at t0; n = 6 at t72 h). 0 vs. 72 h: AlbCre, ***p < 0.0001; AlbCre vs. FGF21Alb-KO: 72 h, ###p < 0.0001. E eWAT and iWAT weight at 1-week (n = 6 except FGF21Alb-KO n = 4). eWAT: AlbCre vs. AlbCre + G49, ***p = 0.0002; FGF21Alb-KO vs. FGF21Alb-KO + G49, ***p = 0.0007; AlbCre vs. FGF21Alb-KO: $$p = 0.0040; AlbCre + G49 vs. FGF21Alb-KO + G49, ##p = 0.0011. iWAT: AlbCre vs. AlbCre + G49, ***p < 0.0001; FGF21Alb-KO vs. FGF21Alb-KO + G49, ***p = 0.0005; AlbCre + G49 vs. FGF21Alb-KO + G49, ##p = 0.0021. F Representative BAT UCP1 images (n = 3). Scale bar 100 µm. Western Blot and quantification (AlbCre n = 9, AlbCre + G49, n = 9; FGF21Alb-KO n = 7, FGF21Alb-KO + G49, n = 10) at 1 week. AlbCre vs. AlbCre + G49, **p = 0.0097; AlbCre + G49 vs. FGF21Alb-KO + G49, #p = 0.0292. G Representative thermography images and maximal BAT temperature (n = 5 AlbCre + G49; n = 5 FGF21Alb-KO + G49), ##p = 0.0014. Unpaired two-tailed t-test. H Plasma FGF21 (AlbCre + G49 t0 and 72 h, n = 6, FGF21Alb-KO + G49 t0 h, n = 9 and 72 h, n = 10) AlbCre +G49 t0 h vs. AlbCre + G49 72 h, ***p < 0.0001; FGF21Alb-KO+G49 t0 h vs. FGF21Alb-KO +  G49 72 h, p = 0.0520; AlbCre +G49 t0 h vs. FGF21Alb-KO+G49 t0 h, $$p = 0.0020; AlbCre + G49 72 h vs. FGF21Alb-KO + G49 72 h, ###p < 0.0001. I Fgf21 in eWAT (AlbCre, AlbCre + G49 n = 6; FGF21Alb-KO n = 4, FGF21Alb-KO + G49 n = 5), iWAT (AlbCre n = 6, AlbCre + G49 n = 5; FGF21Alb-KO n = 4, FGF21Alb-KO + G49 n = 6) and BAT (AlbCre n = 5, AlbCre + G49 n = 6; FGF21Alb-KO n = 5, FGF21Alb-KO + G49 n = 6) at 72 h. eWAT: FGF21Alb-KO vs. FGF21Alb-KO + G49, ***p < 0.0001; AlbCre + G49 vs. FGF21Alb-KO + G49, ###p < 0.0001. iWAT: FGF21Alb-KO vs. FGF21Alb-KO + G49, **p = 0.0033; AlbCre + G49 vs. FGF21Alb-KO + G49, #p = 0.0282. BAT: AlbCre vs. + AlbCre G49, *p = 0.0325; AlbCre + G49 vs. FGF21Alb-KO + G49, #p = 0.0143. Two-way ANOVA with Bonferroni post hoc test in (A (middle), B–F, H, I). J–M FGF21Alb-KO mice received recombinant murine FGF21 at 48, 60 and 72 h post-G49 injection. J Plasma FGF21 (FGF21Alb-KO n = 4, FGF21Alb-KO + G49, n = 5, FGF21Alb-KO + G49 + FGF21, n = 6). FGF21Alb-KO vs. FGF21Alb-KO + G49, *p = 0.0221; FGF21Alb-KO vs. FGF21Alb-KO + G49 + FGF21, ***p < 0.0001; FGF21Alb-KO + G49 vs. FGF21Alb-KO + G49 + FGF21, ###p < 0.0001. Brown–Forsythe and Welch ANOVA with Dunnet’s T3 post hoc test. K BW (FGF21Alb-KO n = 4, FGF21Alb-KO + G49, n = 6, FGF21Alb-KO + G49 + FGF21, n = 6). Two-way RM ANOVA with Bonferroni post hoc test. p values are detailed in Source data file. L Representative BAT UCP1 Western blot and quantification (FGF21Alb-KO n = 5, FGF21Alb-KO + G49, n = 6, FGF21Alb-KO + G49 + FGF21, n = 6). FGF21Alb-KO vs. FGF21Alb-KO + G49 + FGF21, ***p < 0.0001; FGF21Alb-KO + G49 vs. FGF21Alb-KO + G49 + FGF21, ###p < 0.0001. M BAT temperature (FGF21Alb-KO n = 3, FGF21Alb-KO + G49, n = 4, FGF21Alb-KO + G49 + FGF21, n = 5). FGF21Alb-KO vs. FGF21Alb-KO + G49 + FGF21, ***p = 0.0002; FGF21Alb-KO + G49 vs. FGF21Alb-KO + G49 + FGF21, ###p = 0.0008. One-way ANOVA with Bonferroni post hoc test in (L, M). Data are mean ± SEM. Source data are provided as a Source Data file.

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