Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model
Besides structural alterations in the myocardium, heart failure with preserved ejection fraction (HFpEF) is also associated with molecular and physiological alterations of the peripheral skeletal muscles (SKM) contributing to exercise intolerance often seen in HFpEF patients. Recently, the use of So...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/10989 |
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| author | Ephraim B. Winzer Antje Schauer Erik Langner Antje Augstein Keita Goto Anita Männel Peggy Barthel Anett Jannasch Siegfried Labeit Norman Mangner Axel Linke Volker Adams |
| author_facet | Ephraim B. Winzer Antje Schauer Erik Langner Antje Augstein Keita Goto Anita Männel Peggy Barthel Anett Jannasch Siegfried Labeit Norman Mangner Axel Linke Volker Adams |
| author_sort | Ephraim B. Winzer |
| collection | DOAJ |
| description | Besides structural alterations in the myocardium, heart failure with preserved ejection fraction (HFpEF) is also associated with molecular and physiological alterations of the peripheral skeletal muscles (SKM) contributing to exercise intolerance often seen in HFpEF patients. Recently, the use of Sodium-Glucose-Transporter 2 inhibitors (SGLT2i) in clinical studies provided evidence for a significant reduction in the combined risk of cardiovascular death or hospitalization for HFpEF. The present study aimed to further elucidate the impact of Empagliflozin (Empa) on: (1) SKM function and metabolism and (2) mitochondrial function in an established HFpEF rat model. At the age of 24 weeks, obese ZSF1 rats were randomized either receiving standard care or Empa in the drinking water. ZSF1 lean animals served as healthy controls. After 8 weeks of treatment, echocardiography and SKM contractility were performed. Mitochondrial function was assessed in saponin skinned fibers and SKM tissue was snap frozen for molecular analyses. HFpEF was evident in the obese animals when compared to lean—increased E/é and preserved left ventricular ejection fraction. Empa treatment significantly improved E/é and resulted in improved SKM contractility with reduced intramuscular lipid content. Better mitochondrial function (mainly in complex IV) with only minor modulation of atrophy-related proteins was seen after Empa treatment. The results clearly documented a beneficial effect of Empa on SKM function in the present HFpEF model. These effects were accompanied by positive effects on mitochondrial function possibly modulating SKM function. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:18Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a3cc5cc6e3854b2291c98bd59f4067102023-11-23T20:25:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191098910.3390/ijms231910989Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat ModelEphraim B. Winzer0Antje Schauer1Erik Langner2Antje Augstein3Keita Goto4Anita Männel5Peggy Barthel6Anett Jannasch7Siegfried Labeit8Norman Mangner9Axel Linke10Volker Adams11Laboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyDepartment of Cardiac Surgery, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyMedical Faculty Mannheim, University of Heidelberg, 69117 Heidelberg, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, GermanyBesides structural alterations in the myocardium, heart failure with preserved ejection fraction (HFpEF) is also associated with molecular and physiological alterations of the peripheral skeletal muscles (SKM) contributing to exercise intolerance often seen in HFpEF patients. Recently, the use of Sodium-Glucose-Transporter 2 inhibitors (SGLT2i) in clinical studies provided evidence for a significant reduction in the combined risk of cardiovascular death or hospitalization for HFpEF. The present study aimed to further elucidate the impact of Empagliflozin (Empa) on: (1) SKM function and metabolism and (2) mitochondrial function in an established HFpEF rat model. At the age of 24 weeks, obese ZSF1 rats were randomized either receiving standard care or Empa in the drinking water. ZSF1 lean animals served as healthy controls. After 8 weeks of treatment, echocardiography and SKM contractility were performed. Mitochondrial function was assessed in saponin skinned fibers and SKM tissue was snap frozen for molecular analyses. HFpEF was evident in the obese animals when compared to lean—increased E/é and preserved left ventricular ejection fraction. Empa treatment significantly improved E/é and resulted in improved SKM contractility with reduced intramuscular lipid content. Better mitochondrial function (mainly in complex IV) with only minor modulation of atrophy-related proteins was seen after Empa treatment. The results clearly documented a beneficial effect of Empa on SKM function in the present HFpEF model. These effects were accompanied by positive effects on mitochondrial function possibly modulating SKM function.https://www.mdpi.com/1422-0067/23/19/10989HFpEFZSF1SGLT2 inhibitorMuRF1skeletal muscle dysfunctionmuscle atrophy |
| spellingShingle | Ephraim B. Winzer Antje Schauer Erik Langner Antje Augstein Keita Goto Anita Männel Peggy Barthel Anett Jannasch Siegfried Labeit Norman Mangner Axel Linke Volker Adams Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model International Journal of Molecular Sciences HFpEF ZSF1 SGLT2 inhibitor MuRF1 skeletal muscle dysfunction muscle atrophy |
| title | Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model |
| title_full | Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model |
| title_fullStr | Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model |
| title_full_unstemmed | Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model |
| title_short | Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model |
| title_sort | empagliflozin preserves skeletal muscle function in a hfpef rat model |
| topic | HFpEF ZSF1 SGLT2 inhibitor MuRF1 skeletal muscle dysfunction muscle atrophy |
| url | https://www.mdpi.com/1422-0067/23/19/10989 |
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