Fig. 4: Effect of 1-week treatment of DIO mice with G49 in BAT. | Nature Communications

Fig. 4: Effect of 1-week treatment of DIO mice with G49 in BAT.

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

Fig. 4: Effect of 1-week treatment of DIO mice with G49 in BAT.The alternative text for this image may have been generated using AI.

A Representative thermography images and maximal BAT temperature (HFD, n = 9; H + G49, n = 11). HFD vs. H + G49: final, ***p = 0.0006; Initial vs. final: H + G49, +++p < 0.0001. Two-way ANOVA with Bonferroni post hoc test. B Thermogenic-related genes in BAT at 1 week: Cpt1b (HFD n = 7; H + G49, n = 8), ***p < 0.0001; Dio2 (HFD n = 7; H + G49, n = 6), ***p < 0.0001; CoxIVi1 (HFD, H + G49, n = 7), ***p < 0.0001; Ucp1 (HFD n = 9, H + G49, n = 10), ***p = 0.0003; Th (HFD, H + G49, n = 7), *p = 0.0128; Fgf21 (HFD, n = 6; H + G49, n = 7), *p = 0.0242. Unpaired two-tailed t-test. C Representative BAT UCP1 images at 1 week (n = 4). Scale bar 200 µm. D Representative Western blots and quantification. UCP1 (HFD n = 17; H + G49, n = 18), ***p < 0.0001. TH (HFD n = 17; H + G49, n = 21), ***p < 0.0001. Unpaired two-tailed t-test. E Energy expenditure (EE) (n = 4 HFD; H + G49). Light: HFD vs. H + G49: day 2, ***p = 0.0004; day 3, ***p < 0.0001. day 0 vs. day 2: H + G49, +++p < 0.0001. day 0 vs. day 3: H + G49, +++p < 0.0001. Dark: HFD vs. H + G49: day 2, ***p < 0.0001; day 3, ***p < 0.0001. day 0 vs. day 2: H + G49, +++p = 0.0001. day 0 vs. day 3: HFD, +p = 0.0177; H + G49, +++p < 0.0001. Two-way ANOVA with Bonferroni post hoc test. F Seahorse in BAT explants from mice treated 72 h with G49 (HFD, n = 6; H + G49, n = 8 explants from independent mice). Basal, *p = 0.0101; Maximal, *p = 0.0151. Unpaired two-tailed t-test. G BW evolution in UCP1+/+ and UCP1−/− mice (UCP1+/+ n = 8, UCP1+/+ + G49, n = 9; UCP1−/− n = 4, UCP1−/− + G49, n = 5). Mixed-effect analysis test with Bonferroni post hoc test. p values detailed in Source data file. H Plasma FFAs at 6 h (n = 5 at 0 h; n = 5 at 6 h, same mice). UCP1−/− vs. UCP1−/− + G49: 6 h, ***p < 0.0001; 0 h vs. 6 h: UCP1−/− + G49, +++p < 0.0001. Plasma FGF21 at 72 h (UCP1+/+ n = 6, UCP1+/+ + G49, n = 6; UCP1−/− n = 5, UCP1−/− + G49, n = 6). Vehicle vs. G49: UCP1+/+, ***p < 0.0001; UCP1−/−, ***p < 0.0001; UCP1+/+ + G49 vs. UCP1−/− + G49, ###p < 0.0001. Two-way ANOVA with Bonferroni post hoc test. UCP1+/+ vs. UCP1−/−, $p = 0.0409 with unpaired two-tailed t-test. I Representative thermography images and maximal BAT temperature after 1-week (UCP1+/+ n = 5, UCP1+/+ + G49, n = 5; UCP1−/− n = 4, UCP1−/− + G49, n = 5). UCP1+/+ vs. UCP1+/+ + G49, ***p < 0.0001; UCP1+/+ vs. UCP1−/−, $p = 0.0103; UCP1+/+ + G49 vs. UCP1−/− + G49, ###p < 0.0001. Two-way ANOVA with Bonferroni post hoc test. J Beiging-related genes at 1 week (Cidea, HFD, n = 5; H + G49, n = 7, *p = 0.0303. Prdm16, HFD, n = 6; H + G49, n = 7, *p = 0.0416. CoxIVi1, HFD, n = 5; H + G49, n = 7, ***p = 0.0005. Vegf, HFD, n = 8; H + G49, n = 8, ***p = 0.0005. Ucp1, HFD, n = 7; H + G49, n = 9, **p = 0.0064. Th, HFD, n = 6; H + G49, n = 7, **p = 0.0047. Cpt1a, HFD, n = 7; H + G49, n = 7, ***p = 0.0004. Unpaired two-tailed t-test. K eWAT UCP1 representative Western blot and quantification (HFD, n = 15; H + G49, n = 20, ***p < 0.0001) and TH (HFD, n = 7, H + G49; n = 8, **p = 0.0018). Unpaired two-tailed t-test. Representative eWAT UCP1 images (n = 4). Scale bar 100 µm. L Representative iWAT UCP1 Western blot and quantification (HFD, n = 9; H + G49, n = 13). **p = 0.0029. Unpaired two-tailed t-test. Representative iWAT UCP1 images (n = 4). Scale bar 100 µm. Data are mean ± SEM. Source data are provided as a Source Data file.

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