Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF
Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine...
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MDPI AG
2024-03-01
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| author | Paula Ketilly Nascimento Alves Antje Schauer Antje Augstein Maria-Elisa Prieto Jarabo Anita Männel Peggy Barthel Beatrice Vahle Anselmo S. Moriscot Axel Linke Volker Adams |
| author_facet | Paula Ketilly Nascimento Alves Antje Schauer Antje Augstein Maria-Elisa Prieto Jarabo Anita Männel Peggy Barthel Beatrice Vahle Anselmo S. Moriscot Axel Linke Volker Adams |
| author_sort | Paula Ketilly Nascimento Alves |
| collection | DOAJ |
| description | Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine supplementation in both a primary and a secondary prevention approach on SKM function and factors modulating muscle function in an established HFpEF rat model. Female ZSF1 obese rats were randomized to an untreated, a primary prevention, and a secondary prevention group. For primary prevention, leucine supplementation was started before the onset of HFpEF (8 weeks of age) and for secondary prevention, leucine supplementation was started after the onset of HFpEF (20 weeks of age). SKM function was assessed at an age of 32 weeks, and SKM tissue was collected for the assessment of mitochondrial function and histological and molecular analyses. Leucine supplementation prevented the development of SKM dysfunction whereas it could not reverse it. In the primary prevention group, mitochondrial function improved and higher expressions of mitofilin, Mfn-2, Fis1, and miCK were evident in SKM. The expression of UCP3 was reduced whereas the mitochondrial content and markers for catabolism (MuRF1, MAFBx), muscle cross-sectional area, and SKM mass did not change. Our data show that leucine supplementation prevented the development of skeletal muscle dysfunction in a rat model of HFpEF, which may be mediated by improving mitochondrial function through modulating energy transfer. |
| first_indexed | 2024-04-24T18:27:02Z |
| format | Article |
| id | doaj.art-91bf909989d0437293f878b72401bdf3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-24T18:27:02Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-91bf909989d0437293f878b72401bdf32024-03-27T13:30:36ZengMDPI AGCells2073-44092024-03-0113650210.3390/cells13060502Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEFPaula Ketilly Nascimento Alves0Antje Schauer1Antje Augstein2Maria-Elisa Prieto Jarabo3Anita Männel4Peggy Barthel5Beatrice Vahle6Anselmo S. Moriscot7Axel Linke8Volker Adams9Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo 05508000, BrazilHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, GermanyHeart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine supplementation in both a primary and a secondary prevention approach on SKM function and factors modulating muscle function in an established HFpEF rat model. Female ZSF1 obese rats were randomized to an untreated, a primary prevention, and a secondary prevention group. For primary prevention, leucine supplementation was started before the onset of HFpEF (8 weeks of age) and for secondary prevention, leucine supplementation was started after the onset of HFpEF (20 weeks of age). SKM function was assessed at an age of 32 weeks, and SKM tissue was collected for the assessment of mitochondrial function and histological and molecular analyses. Leucine supplementation prevented the development of SKM dysfunction whereas it could not reverse it. In the primary prevention group, mitochondrial function improved and higher expressions of mitofilin, Mfn-2, Fis1, and miCK were evident in SKM. The expression of UCP3 was reduced whereas the mitochondrial content and markers for catabolism (MuRF1, MAFBx), muscle cross-sectional area, and SKM mass did not change. Our data show that leucine supplementation prevented the development of skeletal muscle dysfunction in a rat model of HFpEF, which may be mediated by improving mitochondrial function through modulating energy transfer.https://www.mdpi.com/2073-4409/13/6/502HFpEFZSF1leucinemitochondriadiastolic dysfunctionskeletal muscle dysfunction |
| spellingShingle | Paula Ketilly Nascimento Alves Antje Schauer Antje Augstein Maria-Elisa Prieto Jarabo Anita Männel Peggy Barthel Beatrice Vahle Anselmo S. Moriscot Axel Linke Volker Adams Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF Cells HFpEF ZSF1 leucine mitochondria diastolic dysfunction skeletal muscle dysfunction |
| title | Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF |
| title_full | Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF |
| title_fullStr | Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF |
| title_full_unstemmed | Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF |
| title_short | Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF |
| title_sort | leucine supplementation prevents the development of skeletal muscle dysfunction in a rat model of hfpef |
| topic | HFpEF ZSF1 leucine mitochondria diastolic dysfunction skeletal muscle dysfunction |
| url | https://www.mdpi.com/2073-4409/13/6/502 |
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