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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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Main Authors: Winzer, Ephraim Bernhard (Author) , Schauer, Antje (Author) , Langner, Erik (Author) , Augstein, Antje (Author) , Goto, Keita (Author) , Männel, Anita (Author) , Barthel, Peggy (Author) , Jannasch, Anett (Author) , Labeit, Siegfried (Author) , Mangner, Norman (Author) , Linke, Axel (Author) , Adams, Volker (Author)
Format: Article (Journal)
Language:English
Published: 20 September 2022
In: International journal of molecular sciences
Year: 2022, Volume: 23, Issue: 19, Pages: 1-21
ISSN:1422-0067
DOI:10.3390/ijms231910989
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms231910989
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/23/19/10989
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Author Notes:Ephraim B. Winzer, Antje Schauer, Erik Langner, Antje Augstein, Keita Goto, Anita Männel, Peggy Barthel, Anett Jannasch, Siegfried Labeit, Norman Mangner, Axel Linke and Volker Adams
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Summary: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.
Item Description:Dieser Artikel gehört zum Special issue: Muscle atrophy: from bench to bedside
Gesehen am 11.09.2023
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms231910989

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