Extended Data Fig. 3: Cardiac-specific TGR5 deletion aggravates cardiac dysfunction and cardiolipotoxicity in db/db mice.
From: Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy
a, Experimental scheme for generating db/db;αMHC-Tgr5fl/fl mice (db/db TGR5ΔCM). Mice aged 20 weeks were used in the following experiments. Created with BioRender.com with modifications. b–f, Left ventricular GLS was calculated by Vevo Software (b). n = 6. Ratio of flow Doppler E wave amplitude to tissue Doppler E′ wave amplitude (E/E’) (c). n = 6. Representative left ventricular M-mode echocardiographic images (d). Quantification of left ventricular EF (e). n = 6. Quantification of left ventricular FS (f). n = 6. g–j, Representative Oil Red O (above) and BODIPY 493/503 staining (below, green color) images of cardiac tissues from db/db TGR5fl/fl and db/db TGR5ΔCM mice (g). Scale bar, 50 μm for Oil Red O staining; 10 μm for BODIPY 493/503 staining. The nucleus was stained with DAPI (blue color). Quantitative analysis of Oil Red O staining (h) and BODIPY intensity (i) by Image J. n = 6. Quantitative analysis of intracardiac TG levels (j). n = 6. k–m, Heat map (left) and quantitative analysis (right) of lipid-targeted metabolomic of cardiac tissues from db/db TGR5fl/fl and db/db TGR5ΔCM mice at 20 weeks (k). n = 6. Red indicates upregulation and blue indicates downregulation. The columns and rows represent experimental heart samples and lipid species, respectively. Quantitative analysis of FFA levels in cardiac tissues from TGR5fl/fl and TGR5ΔCM mice in db/m or db/db background at 20 weeks (l). n = 6. FFA species in db/db TGR5fl/fl and db/db TGR5ΔCM mice (m). n = 6. Data are presented as mean ± SEM. Statistical significance was evaluated by two-tailed unpaired Student’s t-test (h,i,k,m) or two-way ANOVA followed by Tukey’s post-hoc test (b,c,e,f,j,l).