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Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction
AIMS: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeutic targets for this complex clinical syndrom...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153641/ https://www.ncbi.nlm.nih.gov/pubmed/36626303 http://dx.doi.org/10.1093/cvr/cvad005 |
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author | Ragni, Maurizio Greco, Carolina Magdalen Felicetta, Arianna Ren, Shuxun Vincent Kunderfranco, Paolo Ruocco, Chiara Carullo, Pierluigi Larcher, Veronica Tedesco, Laura Severi, Ilenia Giordano, Antonio Cinti, Saverio Valerio, Alessandra Sun, Haipeng Wang, Yibin Gao, Chen Condorelli, Gianluigi Nisoli, Enzo |
author_facet | Ragni, Maurizio Greco, Carolina Magdalen Felicetta, Arianna Ren, Shuxun Vincent Kunderfranco, Paolo Ruocco, Chiara Carullo, Pierluigi Larcher, Veronica Tedesco, Laura Severi, Ilenia Giordano, Antonio Cinti, Saverio Valerio, Alessandra Sun, Haipeng Wang, Yibin Gao, Chen Condorelli, Gianluigi Nisoli, Enzo |
author_sort | Ragni, Maurizio |
collection | PubMed |
description | AIMS: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeutic targets for this complex clinical syndrome. We aim to study the molecular mechanisms and effects on cardiac function in rodents with HFrEF of a designer diet in which free essential amino acids—in specifically designed percentages—substituted for protein. METHODS AND RESULTS: Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricle (LV) pressure overload or sham surgery. Whole-body glucose homeostasis was studied with glucose tolerance test, while myocardial dysfunction and fibrosis were measured with echocardiogram and histological analysis. Mitochondrial bioenergetics and morphology were investigated with oxygen consumption rate measurement and electron microscopy evaluation. Circulating and cardiac non-targeted metabolite profiles were analyzed by ultrahigh performance liquid chromatography-tandem mass spectroscopy, while RNA-sequencing was used to identify signalling pathways mainly affected. The amino acid-substituted diet shows remarkable preventive and therapeutic effects. This dietary approach corrects the whole-body glucose metabolism and restores the unbalanced metabolic substrate usage—by improving mitochondrial fuel oxidation—in the failing heart. In particular, biochemical, molecular, and genetic approaches suggest that renormalization of branched-chain amino acid oxidation in cardiac tissue, which is suppressed in HFrEF, plays a relevant role. Beyond the changes of systemic metabolism, cell-autonomous processes may explain at least in part the diet’s cardioprotective impact. CONCLUSION: Collectively, these results suggest that manipulation of dietary amino acids, and especially essential amino acids, is a potential adjuvant therapeutic strategy to treat systolic dysfunction and HFrEF in humans. |
format | Online Article Text |
id | pubmed-10153641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101536412023-05-03 Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction Ragni, Maurizio Greco, Carolina Magdalen Felicetta, Arianna Ren, Shuxun Vincent Kunderfranco, Paolo Ruocco, Chiara Carullo, Pierluigi Larcher, Veronica Tedesco, Laura Severi, Ilenia Giordano, Antonio Cinti, Saverio Valerio, Alessandra Sun, Haipeng Wang, Yibin Gao, Chen Condorelli, Gianluigi Nisoli, Enzo Cardiovasc Res Original Article AIMS: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeutic targets for this complex clinical syndrome. We aim to study the molecular mechanisms and effects on cardiac function in rodents with HFrEF of a designer diet in which free essential amino acids—in specifically designed percentages—substituted for protein. METHODS AND RESULTS: Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricle (LV) pressure overload or sham surgery. Whole-body glucose homeostasis was studied with glucose tolerance test, while myocardial dysfunction and fibrosis were measured with echocardiogram and histological analysis. Mitochondrial bioenergetics and morphology were investigated with oxygen consumption rate measurement and electron microscopy evaluation. Circulating and cardiac non-targeted metabolite profiles were analyzed by ultrahigh performance liquid chromatography-tandem mass spectroscopy, while RNA-sequencing was used to identify signalling pathways mainly affected. The amino acid-substituted diet shows remarkable preventive and therapeutic effects. This dietary approach corrects the whole-body glucose metabolism and restores the unbalanced metabolic substrate usage—by improving mitochondrial fuel oxidation—in the failing heart. In particular, biochemical, molecular, and genetic approaches suggest that renormalization of branched-chain amino acid oxidation in cardiac tissue, which is suppressed in HFrEF, plays a relevant role. Beyond the changes of systemic metabolism, cell-autonomous processes may explain at least in part the diet’s cardioprotective impact. CONCLUSION: Collectively, these results suggest that manipulation of dietary amino acids, and especially essential amino acids, is a potential adjuvant therapeutic strategy to treat systolic dysfunction and HFrEF in humans. Oxford University Press 2023-01-10 /pmc/articles/PMC10153641/ /pubmed/36626303 http://dx.doi.org/10.1093/cvr/cvad005 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Ragni, Maurizio Greco, Carolina Magdalen Felicetta, Arianna Ren, Shuxun Vincent Kunderfranco, Paolo Ruocco, Chiara Carullo, Pierluigi Larcher, Veronica Tedesco, Laura Severi, Ilenia Giordano, Antonio Cinti, Saverio Valerio, Alessandra Sun, Haipeng Wang, Yibin Gao, Chen Condorelli, Gianluigi Nisoli, Enzo Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction |
title | Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction |
title_full | Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction |
title_fullStr | Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction |
title_full_unstemmed | Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction |
title_short | Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction |
title_sort | dietary essential amino acids for the treatment of heart failure with reduced ejection fraction |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153641/ https://www.ncbi.nlm.nih.gov/pubmed/36626303 http://dx.doi.org/10.1093/cvr/cvad005 |
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