Empagliflozin and Liraglutide Differentially Modulate Cardiac Metabolism in Diabetic Cardiomyopathy in Rats
Abstract
:1. Introduction
2. Results
2.1. Effects of Empagliflozin and Liraglutide on Biochemistry, BP, Myocardial Function, and Heart Size
2.2. Effects of Empagliflozin and Liraglutide on Myocardial Fatty Acid Metabolism
2.3. Effects of Empagliflozin and Liraglutide on Myocardial Glucose Metabolism
2.4. Effects of Empagliflozin and Liraglutide on Myocardial Inflammatory Cytokines
2.5. Effects of Empagliflozin and Liraglutide on Myocardial Fibrosis and Apoptosis
2.6. Combined Effects of Empagliflozin and Liraglutide in DCM
3. Discussion
4. Methods
4.1. Animal Models and Tissue Preparations
4.2. Blood Sampling and Biochemical Measurements
4.3. Hemodynamic Studies: BP and Echocardiogram Measurements
4.4. Histopathological Examination of Cardiomyocytes
4.5. Western Blot Analysis
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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CON | DM | DM + EMPA | DM+LIRA | |
---|---|---|---|---|
FBS (mg/dL) | ||||
2 weeks after STZ injection | 109.8 ± 1.1 | 398.6 ± 11.7 * | 394.5 ± 8.9 * | 395.9 ± 3.6 * |
4 weeks after treatment | 113 ± 2.9 | 429.5 ± 20.2 * | 151.8 ± 10.4 # | 284.9 ± 25.1 *#§ |
Biochemical values after treatment | ||||
TG (mg/dL) | 84.9 ± 6.0 | 144.3 ± 25.5 | 74.4 ± 19.9 # | 98.9 ± 13.9 |
TC (mg/dL) | 52.8 ± 3.6 | 60.6 ± 4.2 | 50.5 ± 3.7 | 52.3 ± 2.9 |
HDL-C (mg/dL) | 22.8 ± 1.1 | 27.9 ± 1.7 * | 23.5 ± 0.8 | 26.2 ± 1.5 |
LDL-C (mg/dL) | 4.1 ± 0.4 | 6.3 ± 0.9 * | 3.9 ± 0.2 # | 2.8 ± 0.3 # |
FFAs (µg/dL) | 0.7 ± 0.0 | 1.0 ± 0.2 * | 0.6 ± 0.0 # | 0.6 ± 0.1 # |
ST2 (pg/mL) | 296.2 ± 39.1 | 455.1 ± 54.7 * | 292.5 ± 18.7 # | 295.3 ± 42.9 # |
BP and HR after treatment | ||||
SBP (mmHg) | 127.8 ± 5.5 | 113.5 ± 5.4 | 118.3 ± 11.7 | 116.5 ± 6.9 |
DBP (mmHg) | 73.9 ± 4.4 | 65.3 ± 5.3 | 75.9 ± 9.3 | 60.5 ± 6.4 |
HR (bpm) | 440 ± 13.9 | 311.6 ± 19.7 * | 367.1 ± 24.6 | 387.4 ± 21.0 |
Weight | ||||
BW 2 weeks after STZ injection (g) | 380.4 ± 4.5 | 368.0 ± 14.2 | 368.8 ± 9.5 | 369.0 ± 6.6 |
BW after treatment (g) | 543.8 ± 5.6 | 379.1 ± 10.2 * | 441.9 ± 17.3 *# | 402.9 ± 15.5 * |
HW (g) | 1.6 ± 0.0 | 1.4 ± 0.0 * | 1.6 ± 0.0 # | 1.3 ± 0.0 *§ |
HW/BW (mg/g) | 3.2 ± 0.0 | 4.2 ± 0.2 * | 3.6 ± 0.1 # | 3.3 ± 0.1 # |
DM + EMPA | DM + LIRA | DM + EMPA + LIRA | |
---|---|---|---|
Echocardiograms | |||
LVEDd (mm) | 6.9 ± 0.5 | 7.1 ± 0.3 | 6.7 ± 0.0 |
LVESd (mm) | 3.4 ± 0.5 | 3.7 ± 0.1 | 3.2 ± 0.2 |
EDV (mL) | 0.8 ± 0.1 | 0.9 ± 0.1 | 0.7 ± 0.1 |
ESV (mL) | 0.09 ± 0.0 | 0.14 ± 0.0 § | 0.07 ± 0.0 ¶ |
IVSd (mm) | 1.9 ± 0.2 | 1.7 ± 0.1 | 1.9 ± 0.0 |
LVPW (mm) | 2.2 ± 0.1 | 1.8 ± 0.1 § | 2.2 ± 0.1 ¶ |
EF (%) | 85.4 ± 3.9 | 81.2 ± 2.2 | 89.3 ± 1.9 |
FS (%) | 48.8 ± 4.4 | 45.1 ± 2.4 | 57.4 ± 2.1 ¶ |
Physical characteristics | |||
HR (bpm) | 407.6 ± 22.6 | 413.4 ± 5.8 | 424 ± 8.6 |
SBP (mmHg) | 119.8 ± 7.8 | 115.8 ± 6.8 | 118.8 ± 4.5 |
DBP (mmHg) | 71.0 ± 6.4 | 61.4 ± 9.2 | 68.8 ± 3.2 |
BW 2 weeks after STZ injection (g) | 355.4 ± 9.6 | 358.4 ± 4.9 | 356.8 ± 3.2 |
BW after treatment (g) | 416.8 ± 17.1 | 327.8 ± 8.4 § | 399 ± 12.6¶ |
HW (g) | 1.6 ± 0.0 | 1.5 ± 0.1 | 1.6 ± 0.1 |
HW/BW (mg/g) | 3.9 ± 0.3 | 4.4 ± 0.2 | 3.6 ± 0.2 |
Biochemical values | |||
FBS 2 weeks after STZ injection (mg/dL) | 396.0 ± 12.4 | 396.6 ± 5.7 | 397.2 ± 12.8 |
FBS after treatment (mg/dL) | 142.4 ± 21.5 | 331.6 ± 22.4 § | 109.6 ± 14.5 ¶ |
TG (mg/dL) | 60.2 ± 16.8 | 86.8 ± 15.6 | 47.0 ± 4.8 |
TC (mg/dL) | 51.8 ± 3.4 | 55.0 ± 3.4 | 55.5 ± 4.6 |
HDL-C (mg/dL) | 23.2 ± 1.3 | 26.0 ± 1.0 | 23.6 ± 1.0 |
LDL-C (mg/dL) | 3.8 ± 0.4 | 3.0 ± 0.3 | 3.8 ± 0.2 |
FFAs (µg/dL) | 0.6 ± 0.0 | 0.7 ± 0.0 | 0.6 ± 0.0 |
ST2 (pg/mL) | 290.2 ± 17.8 | 296.2 ± 38.2 | 281.0 ± 21.2 |
Histopathology | |||
Fibrosis area (%) | 5.3 ± 0.1 | 4.5 ± 0.1 § | 4.3 ± 0.1 § |
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Trang, N.N.; Chung, C.-C.; Lee, T.-W.; Cheng, W.-L.; Kao, Y.-H.; Huang, S.-Y.; Lee, T.-I.; Chen, Y.-J. Empagliflozin and Liraglutide Differentially Modulate Cardiac Metabolism in Diabetic Cardiomyopathy in Rats. Int. J. Mol. Sci. 2021, 22, 1177. https://doi.org/10.3390/ijms22031177
Trang NN, Chung C-C, Lee T-W, Cheng W-L, Kao Y-H, Huang S-Y, Lee T-I, Chen Y-J. Empagliflozin and Liraglutide Differentially Modulate Cardiac Metabolism in Diabetic Cardiomyopathy in Rats. International Journal of Molecular Sciences. 2021; 22(3):1177. https://doi.org/10.3390/ijms22031177
Chicago/Turabian StyleTrang, Nguyen Ngoc, Cheng-Chih Chung, Ting-Wei Lee, Wan-Li Cheng, Yu-Hsun Kao, Shih-Yu Huang, Ting-I Lee, and Yi-Jen Chen. 2021. "Empagliflozin and Liraglutide Differentially Modulate Cardiac Metabolism in Diabetic Cardiomyopathy in Rats" International Journal of Molecular Sciences 22, no. 3: 1177. https://doi.org/10.3390/ijms22031177