Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training

Abstract Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants...

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Autores principales:	Louise Y. Takeshita, Peter K. Davidsen, John M. Herbert, Philipp Antczak, Matthijs K. C. Hesselink, Patrick Schrauwen, S. John Weisnagel, Jeremy M. Robbins, Robert E. Gerszten, Sujoy Ghosh, Mark A. Sarzynski, Claude Bouchard, Francesco Falciani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a3774b2c4754f49983653dd5d84465b
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spelling	oai:doaj.org-article:9a3774b2c4754f49983653dd5d84465b2021-12-05T12:13:27ZGenomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training10.1038/s41598-021-98792-12045-2322https://doaj.org/article/9a3774b2c4754f49983653dd5d84465b2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98792-1https://doaj.org/toc/2045-2322Abstract Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆) in insulin sensitivity index (Si) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on Si. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline Si and ∆Si, focused around cholinergic signalling, including downstream calcium and chemokine signalling. The identification of calcium regulated MEF2A transcription factor as the most statistically significant candidate driving the transcriptional signature associated to ∆Si further strengthens the relevance of calcium signalling in EET mediated Si response.Louise Y. TakeshitaPeter K. DavidsenJohn M. HerbertPhilipp AntczakMatthijs K. C. HesselinkPatrick SchrauwenS. John WeisnagelJeremy M. RobbinsRobert E. GersztenSujoy GhoshMark A. SarzynskiClaude BouchardFrancesco FalcianiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Louise Y. Takeshita Peter K. Davidsen John M. Herbert Philipp Antczak Matthijs K. C. Hesselink Patrick Schrauwen S. John Weisnagel Jeremy M. Robbins Robert E. Gerszten Sujoy Ghosh Mark A. Sarzynski Claude Bouchard Francesco Falciani Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
description	Abstract Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆) in insulin sensitivity index (Si) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on Si. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline Si and ∆Si, focused around cholinergic signalling, including downstream calcium and chemokine signalling. The identification of calcium regulated MEF2A transcription factor as the most statistically significant candidate driving the transcriptional signature associated to ∆Si further strengthens the relevance of calcium signalling in EET mediated Si response.
format	article
author	Louise Y. Takeshita Peter K. Davidsen John M. Herbert Philipp Antczak Matthijs K. C. Hesselink Patrick Schrauwen S. John Weisnagel Jeremy M. Robbins Robert E. Gerszten Sujoy Ghosh Mark A. Sarzynski Claude Bouchard Francesco Falciani
author_facet	Louise Y. Takeshita Peter K. Davidsen John M. Herbert Philipp Antczak Matthijs K. C. Hesselink Patrick Schrauwen S. John Weisnagel Jeremy M. Robbins Robert E. Gerszten Sujoy Ghosh Mark A. Sarzynski Claude Bouchard Francesco Falciani
author_sort	Louise Y. Takeshita
title	Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
title_short	Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
title_full	Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
title_fullStr	Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
title_full_unstemmed	Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
title_sort	genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9a3774b2c4754f49983653dd5d84465b
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_version_	1718372146415140864

Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training

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