Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model
Abstract
:1. Introduction
2. Results
2.1. Impact of Empaliflozin on Physiological and Echocardiographic Parameter
2.2. Impact of Empaliflozin on Muscle Trophicity and Function
2.3. Impact of Empaliflozin on Muscle Atrophy Marker Expression
2.4. Impact of Empaliflozin on Mitochondrial Function
2.5. Impact of Empaliflozin on Metabolic Key Enzymes
3. Discussion
- Improved skeletal muscle contractility and reduced lipid content with some alterations of atrophy-related proteins;
- Improved mitochondrial function especially in complex IV without modulating the protein expression of mitochondrial complex proteins;
- Had no effect on key enzymes of different metabolic pathways such as ketone body utilization, ß-oxidation or Krebs cycle.
3.1. Empagliflozin and Skeletal Muscle Mass and Function
3.2. Empagliflozin and Mitochondrial Function
3.3. Empagliflozin and Metabolic Alterations
3.4. Study Limitations
4. Materials and Methods
4.1. Study Design
4.2. Echocardiography and Invasive Hemodynamic Measurements
4.3. Skeletal Muscle Function and Cross Sectional Area
4.4. Muscle Mitochondrial Respiration
4.5. Western Blot Analysis
4.6. Enzyme Activity Measurements
4.7. Histological Analysis
4.8. Triglyceride and Glucose Content
4.9. Statistical Analyses
5. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Lean (n = 15) | Obese (n = 12) | Obese + Empa (n = 14) |
---|---|---|---|
Body weight (g) | 255 ± 4 | 532 ± 9 *** | 488 ± 6 ***,§§§ |
Tibia length (TL, mm) | 35.6 ± 0.1 | 35.6 ± 0.1 | 35.3 ± 0.1 |
Heart weight/TL (mg/mm) | 27.75 ± 0.65 | 43.82 ± 2.02 *** | 36.70 ± 1.05 ***,§§§ |
Lung weight (wet/dry) | 4.56 ± 0.02 | 4.22 ± 0.04 *** | 4.22 ± 0.06 *** |
Lung wet weight/TL (mg/mm) | 10.89 ± 0.11 | 11.91 ± 0.21 *** | 11.04 ± 0.18 §§ |
Kidney weight/TL (mg/mm) | 28.2 ± 0.5 | 46.6 ± 1.4 *** | 49.4 ± 1.0 *** |
blood glucose (mmol/L) | 19.9 ± 1.8 | 37.2 ± 1.5 *** | 25.6 ± 0.6 §§§ |
Urinary glucose (mmol/L) | 2.3 ± 0.6 | 15.2 ± 3.8 | 142.5 ± 21.6 ***,§§§ |
Echocardiography/invasive hemodynamic | |||
LVEF (%) | 68.0 ± 1.4 | 67.7 ± 1.7 | 68.0 ± 1.2 |
LVFS (%) | 23.6 ± 1.1 | 24.9 ± 1.1 | 22.9 ± 0.8 |
Aortic blood pressure (mmHg) | 97 ± 3 | 129 ± 3 *** | 117 ± 5 *** |
E/é | 17.5 ± 0.7 | 22.8 ± 1.1 *** | 19.5 ± 0.8 § |
LVEDP (mmHg) | 5.96 ± 0.35 | 8.02 ± 0.61 *** | 7.05 ± 0.37 § |
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Winzer, E.B.; Schauer, A.; Langner, E.; Augstein, A.; Goto, K.; Männel, A.; Barthel, P.; Jannasch, A.; Labeit, S.; Mangner, N.; et al. Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model. Int. J. Mol. Sci. 2022, 23, 10989. https://doi.org/10.3390/ijms231910989
Winzer EB, Schauer A, Langner E, Augstein A, Goto K, Männel A, Barthel P, Jannasch A, Labeit S, Mangner N, et al. Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model. International Journal of Molecular Sciences. 2022; 23(19):10989. https://doi.org/10.3390/ijms231910989
Chicago/Turabian StyleWinzer, Ephraim B., Antje Schauer, Erik Langner, Antje Augstein, Keita Goto, Anita Männel, Peggy Barthel, Anett Jannasch, Siegfried Labeit, Norman Mangner, and et al. 2022. "Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model" International Journal of Molecular Sciences 23, no. 19: 10989. https://doi.org/10.3390/ijms231910989