Fig. 7: Both GCGR and GLP-1R mediate the inter-organ crosstalk and metabolic effects of G49 in DIO mice. | Nature Communications

Fig. 7: Both GCGR and GLP-1R mediate the inter-organ crosstalk and metabolic effects of G49 in DIO mice.

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

Fig. 7: Both GCGR and GLP-1R mediate the inter-organ crosstalk and metabolic effects of G49 in DIO mice.The alternative text for this image may have been generated using AI.

A BW (H + G49, n = 11 and n = 6 in other groups). Two-way RM ANOVA with Bonferroni post hoc test. p values are detailed in Source data file. B Cumulative food intake (n = 4 in all groups). HFD vs. H + GCGRant + G49, ***p < 0.0001; H + G49 vs. H + GCGRant + G49, ###p < 0.0001. One-way ANOVA with Bonferroni post hoc test. C Representative MRI images. D Quantification of total fat and visceral fat (HFD, n = 5; H + G49, n = 4; H + Ex9-39 + G49, n = 5; H + GCGRant + G49, n = 5; H + Ex9-39 + GCGRant + G49, n = 4), eWAT weight (n = 10 in HFD and H + G49; n = 6 for other groups) and iWAT weight (n = 10 in HFD and H + G49; n = 6 in H + Ex9-39 + G49 and H + GCGRant + G49; n = 5 in H + Ex9-39 + GCGRant + G49) at 1 week. Total fat: HFD vs. H + G49, ***p = 0.0002; H + G49 vs. H + Ex9-39 + G49, ###p = 0.0004; H + G49 vs. H + GCGRant + G49, ###p = 0.0003; H + G49 vs. H + Ex9-39 + GCGRant + G49, ###p < 0.0001. Visceral fat: HFD vs. H + G49, **p = 0.0034; H + G49 vs. H + Ex9-39 + G49, ##p = 0.0028; H + G49 vs. H + GCGRant + G49, #p = 0.0102; H + G49 vs. H + Ex9-39 + GCGRant + G49, ###p = 0.0003. eWAT weight: HFD vs. H + G49, ***p = 0.0001; H + G49 vs. H + Ex9-39 + G49, ##p = 0.0028; H + G49 vs. H + GCGRant + G49, ###p < 0.0001; H + G49 vs. H + Ex9-39 + GCGRant + G49, ##p = 0.0037. iWAT weight: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + Ex9-39 + G49, ###p = 0.0006; H + G49 vs. H + GCGRant + G49, ###p < 0.0001; H + G49 vs. H + Ex9-39 + GCGRant + G49, ###p < 0.0001. One-way ANOVA with Bonferroni post hoc test. E eWAT Ucp1 (n = 6 in HFD, H + G49, H + GCGRant + G49 and n = 5 in other groups) and Th (n = 6 in HFD, H  + Ex9-39 + G49 and H  + GCGRant + G49; n = 7 in H + G49; n = 5 in H  + Ex9-39 + GCGRant + G49) mRNAs at 1 week. Ucp1: HFD vs. H + G49, *p = 0.0200; H + G49 vs. H + Ex9-39 + G49, #p = 0.0163; H + G49 vs. H + GCGRant + G49, #p = 0.0175; H + G49 vs. H + Ex9-39 + GCGRant + G49, #p = 0.0139. Th: HFD vs. H + G49, *p = 0.0300; H + G49 vs. H + Ex9-39 + G49, #p = 0.0496; H + G49 vs. H + Ex9-39 + GCGRant + G49, #p = 0.0308. Kruskal–Wallis with Dunn’s post hoc test. F Representative thermographic images and maximal BAT temperature at 1 week (n = 5 in HFD and H + G49; n = 8 in H + Ex9-39 + G49 and H + GCGRant + G49; n = 6 in H + Ex9-39 + GCGRant + G49). HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + Ex9-39 + G49, ###p < 0.0001; H + G49 vs. H + GCGRant + G49, ###p < 0.0001; H + G49 vs. H + Ex9-39 + GCGRant + G49, ###p < 0.0001. One-way ANOVA with Bonferroni post hoc test. G BAT Ucp1 (n = 6 except H + Ex9-39 + G49, n = 7) and Th (HFD, n = 8; H + G49, n = 9; H + Ex9-39 + G49, n = 6; H + GCGRant + G49 and H + Ex9-39 + GCGRant + G49 n = 7) at 1 week. Ucp1: HFD vs. H + G49, **p = 0.0029; H + G49 vs. H + Ex9-39 + G49, ##p = 0.0032; H + G49 vs. H + GCGRant + G49, ###p = 0.0008; H + G49 vs. H + Ex9-39 + GCGRant + G49, ##p = 0.0043. One-way ANOVA with Bonferroni post hoc test. Th: HFD vs. H + G49, ***p = 0.0007; HFD vs. H + GCGRant + G49, **p = 0.0092; H + G49 vs. H + Ex9-39 + G49, ##p = 0.0073; H + G49 vs. H + Ex9-39 + GCGRant + G49, #p = 0.0101. Kruskal–Wallis with Dunn’s post hoc test. H EE at 1 week (n = 4 except in H + G49 in dark n = 5). Light: H + G49 vs. H + Ex9-39 + G49: day 2, #p = 0.0306; day 3, ###p < 0.0001; day 4, ###p < 0.0001; H + G49 vs. H + GCGRant + G49: day 2, ##p = 0.0084; day 3, ###p = 0.0003; day 4, ###p < 0.0001; day 0 vs. day 4: H + G49, ++p = 0.0054. Dark: H + G49 vs. H + Ex9-39 + G49: day 4, ###p < 0.0001; H + G49 vs. H + GCGRant + G49: day 3, #p = 0.0388; day 4, ###p < 0.0001; day 0 vs. day 4: H + G49, +++p < 0.0001. Two-way ANOVA with Bonferroni post hoc test. Data are mean ± SEM. Source data are provided as a Source Data file.

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