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A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation

Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synt...

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Autores principales: Bonilla, Diego A., Moreno, Yurany, Rawson, Eric S., Forero, Diego A., Stout, Jeffrey R., Kerksick, Chad M., Roberts, Michael D., Kreider, Richard B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397972/
https://www.ncbi.nlm.nih.gov/pubmed/34444681
http://dx.doi.org/10.3390/nu13082521
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author Bonilla, Diego A.
Moreno, Yurany
Rawson, Eric S.
Forero, Diego A.
Stout, Jeffrey R.
Kerksick, Chad M.
Roberts, Michael D.
Kreider, Richard B.
author_facet Bonilla, Diego A.
Moreno, Yurany
Rawson, Eric S.
Forero, Diego A.
Stout, Jeffrey R.
Kerksick, Chad M.
Roberts, Michael D.
Kreider, Richard B.
author_sort Bonilla, Diego A.
collection PubMed
description Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose–response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.
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spelling pubmed-83979722021-08-29 A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation Bonilla, Diego A. Moreno, Yurany Rawson, Eric S. Forero, Diego A. Stout, Jeffrey R. Kerksick, Chad M. Roberts, Michael D. Kreider, Richard B. Nutrients Article Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose–response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms. MDPI 2021-07-23 /pmc/articles/PMC8397972/ /pubmed/34444681 http://dx.doi.org/10.3390/nu13082521 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bonilla, Diego A.
Moreno, Yurany
Rawson, Eric S.
Forero, Diego A.
Stout, Jeffrey R.
Kerksick, Chad M.
Roberts, Michael D.
Kreider, Richard B.
A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation
title A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation
title_full A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation
title_fullStr A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation
title_full_unstemmed A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation
title_short A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation
title_sort convergent functional genomics analysis to identify biological regulators mediating effects of creatine supplementation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397972/
https://www.ncbi.nlm.nih.gov/pubmed/34444681
http://dx.doi.org/10.3390/nu13082521
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