Liraglutide combined with HIIT preserves contractile apparatus and blunts the progression of heart failure in diabetic cardiomyopathy rats

Figures

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  Fig. 1. Schematic presentation of the experimental design.

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  Fig. 2. HIIT training program.

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  Fig. 3. Effects of Liragutide and/or HIIT on cardiac diastolic and systolic function. Data were expressed as the mean ± SD. (A,B) E/A ratio > 1.5 and prolonged IVRT means impaired diastolic dysfunction. (C,D) Decreased LVEF and FS means impaired systolic dysfunction. (E,F) Reduced LVPW and IVS means cardiac eccentric hypertrophy. **p < 0.01 compared with the CON group, ##p < 0.01 compared with the DCM group, &p < 0.01 compared with the Lira + HIIT group. E/A ratio the ratio of peak velocity of early LV filling (E-wave), and the peak velocity of late LV filling (A-wave), IVRT isovolumic relaxation time, LVEF left ventricular ejection fraction, FS fractional shortening, LVPW left ventricular posterior wall, IVS interventricular septum.

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  Fig. 4. Liraglutide and/or HIIT alleviated eccentric cardiac hypertrophy. (A) Myocardial HE staining of different groups of rats (×50 magnification). Hearts in the CON group had normal structure; DCM rats exhibited loose structure, large ventricular cavity; hearts after Liraglutide and/or HIIT intervention, indicating closely arranged myocardial cells, similar to the normal heart. (B) HW/BW ratio of heart weight/body weight. (C) CSA cross sectional area. **p < 0.01 compared with the CON group; #p < 0.05 compared with the DCM group; ##p < 0.01 compared with the DCM group, ψp < 0.01 compared with the HIIT group.

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  Fig. 5. Liraglutide and/or HIIT alleviated cardiac remodeling in DCM rats. (A) Upper A panel: Electron microscope images showing the myocardial ultrastructure in different groups of rats (×20,000 magnification), arrows indicate M-line and Z-disc. Lower A panel: Tissue sections were stained with Masson staining (×200 magnification). (B) Quantification of cardiac fibrosis. Data were expressed as the mean ± SD. **p < 0.01 compared with the CON group; ##p < 0.01 compared with the DCM group; Ɨp < 0.05 compared with the Lira group.

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  Fig. 6. The effects of HIIT on cardiac remodeling. (A) α-MHC mRNA relative expression. (B) β-MHC mRNA relative expression. (C) MURF1 mRNA relative expression. (D) FOXO1 mRNA relative expression. Data were expressed as the mean ± SD. **p < 0.01 as compared with CON group; ##p < 0.01 compared with the DCM group. α-MHC Myosin heavy chain-α, β-MHC Myosin heavy chain-β, MURF1 Muscle Ring Finger1, FOXO1 Forkhead Box Protein1.

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  Fig. 7. Combination therapy prevented the colocalization of FOXO1 and MURF1 in diabetic hearts. (A) Immunofluorescence staining of DAPI, FOXO1 and MURF1 (×200 magnification) with co-localization scatter plot within groups. (B) The relative FOXO1 and MURF1 fluorescence intensity normalized to the DAPI fluorescence. (C) The co-localization parameters within groups. Analysis of fluorescence intensity histogram showed that pixels were localized along the y = x line, which indicated an overlap in scatter gram. Pearson’s correlation coefficient and Mander’s colocalization coefficients were utilized to indicate colocation relationship. **p < 0.01 compared with the CON group; ##p < 0.01 compared with the DCM group. Ɨp < 0.01 compared with the HIIT group, ψp < 0.05 compared with the Lira + HIIT group.

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  Fig. 8. The concentration of serum biomarkers of myocardial injury levels in the indicated groups. (A) Serum BNP levels. (B) Serum cTNT levels. (C) Serum GLP-1 level. Data are expressed as the mean ± SD. **p < 0.01 compared with CON group; #p < 0.05 compared with the DCM group; ##p < 0.01 compared with the DCM group. BNP brain natriuretic peptide, cTNT cardiac troponin.

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  Fig. 9. Cardiac GLP-1 and GLP-1R proteins in the indicated groups. Data are expressed as the mean ± SD. *p < 0.05 as compared with the CON group; **p < 0.01 compared with the CON group; #p < 0.05 compared with the DCM group; ##p < 0.01 compared with the DCM group; Ɨp < 0.05 compared with the Lira group; ƗƗp < 0.01 compared with the Lira group.