Document Type
Article
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.
Digital Object Identifier (DOI)
Publication Info
Published in Scientific Reports, Volume 11, 2021.
Rights
© The Author(s) 2021 Tis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
APA Citation
Takeshita, L. Y., Davidsen, P. K., Herbert, J. M., Antczak, P., Hesselink, C., Schrauwen, P., S. John Weisnagel, Robbins, J. M., Gerszten, R. E., Ghosh, S., Sarzynski, M. A., Bouchard, C., & Falciani, F. (2021). Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training. Scientific Reports, 11. https://doi.org/10.1038/s41598-021-98792-1