Fig. 9: ATGLi blocks G49-mediated BAT activation and reduces its effect in body weight loss. | Nature Communications

Fig. 9: ATGLi blocks G49-mediated BAT activation and reduces its effect in body weight loss.

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

Fig. 9

A BW evolution (HFD, n = 4; H + G49, n = 11; H + ATGLi, n = 6; H + G49 + ATGLi, n = 16). Two-way RM ANOVA with Bonferroni post hoc test. p values are detailed in Source data file. Cumulative food intake (HFD, n = 4; H + G49, n = 5; H + ATGLi, n = 4; H + G49 + ATGLi, n = 5). HFD vs. H + G49, **p = 0.0010; H + ATGLi vs. H + G49 + ATGLi, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, #p = 0.0447. B eWAT (HFD, n = 9; H + G49, n = 9; H + ATGLi, n = 6; H + G49 + ATGLi, n = 12) and iWAT (HFD, n = 8; H + G49, n = 9; H+ATGLi, n = 6; H + G49+ATGLi, n = 11) weight at 72 h. eWAT: HFD vs. H + G49, ***p = 0.0001; H + G49 vs. H + G49+ATGLi, ###p < 0.0001. iWAT: HFD vs. H + G49, **p = 0.0022; H + G49 vs. H + G49+ATGLi, ###p < 0.0001. C Plasma FFAs at 6 h (HFD, n = 6; H + G49, n = 9; H+ATGLi, n = 6; H + G49 + ATGLi, n = 11). HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. D Representative MRI images (upper panel) and total and visceral fat (HFD, n = 4; H + G49, n = 5; H + ATGLi, n = 5; H + G49 + ATGLi, n = 4) (lower panel). Total fat: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. Visceral fat: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. E Representative eWAT H&E images (scale bar 500 µm) (n = 5) and immune cells in SVF at 6 h (Cd11c−Cd206+ and Cd11c+Cd206−: HFD, n = 5; H + G49, n = 6; H + ATGLi, n = 5; H + G49 + ATGLi, n = 7; TCRβ+NK1.1+ and SiglecF+: HFD, n = 5; H + G49, n = 7; H + ATGLi, n = 5; H + G49 + ATGLi, n = 7). Cd11c−Cd206+: HFD vs. H+G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. Cd11c+Cd206−: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p = 0.0006. TCRβ+NK1.1+: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p = 0.0002. SiglecF+: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. F Plasma insulin (H + G49, t0, 6 h, n = 6; H + G49 + ATGLi t0 h, n = 6, t6 h, n = 11). 0 h vs. 6 h: H + G49, ***p < 0.0001; H + G49 + ATGLi, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi: 6 h, ###p < 0.0001. G Representative H&E images (scale bar 250 µm) (n = 4) and mRNAs in liver at 6 h (Srebf1, HFD, n = 5; H + G49, n = 6; H+ATGLi, n = 5; H + G49+ATGLi, n = 6; Fasn; HFD, n = 5; H + G49, n = 6; H+ATGLi, n = 5; H + G49 + ATGLi, n = 7). Srebf1: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. Fasn: HFD vs. H + G49, ***p < 0.0001; H + ATGLi vs. H + G49 + ATGLi, *p = 0.0233; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. H Cpt1a (HFD, n = 5; H + G49, n = 6; H + ATGLi, n = 5; H + G49 + ATGLi, n = 6), Hmcs2 (HFD, n = 4; H + G49, n = 5; H + ATGLi, n = 4; H + G49 + ATGLi, n = 6) and blood ketone bodies (HFD, n = 5; H + G49, n = 6; H + ATGLi, n = 5; H + G49 + ATGLi, n = 6) at 72 h. Cpt1a: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49 + ATGLi, ###p < 0.0001. Hmcs2: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49+ATGLi, ###p < 0.0001. Blood ketone bodies: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49+ATGLi, ###p < 0.0001. I Fgf21 at 72 h (HFD, n = 4; H + G49, n = 5; H+ATGLi, n = 4; H + G49+ATGLi, n = 6) HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49+ATGLi, ###p < 0.0001. J BAT Ucp1 (n = 5 except H + G49+ATGLi n = 11), representative UCP1 Western blot and quantification (n = 6 in all groups) and representative BAT UCP1 images (Scale bar 250 µm) (n = 3) at 72 h. Ucp1: HFD vs. H + G49, ***p < 0.0001; H + G49 vs. H + G49+ATGLi, ###p < 0.0001. UCP1 protein levels: HFD vs. H + G49, ***p = 0.0007; H + G49 vs. H + G49ATGLi, ##p = 0.0058. K Representative thermographic images and quantification of Δ maximal BAT temperature (n = 4 in A (right)–K Two-way ANOVA with Bonferroni post hoc test. Source data are provided as a Source Data file.

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