@article{4a00ddf28c42412e88a56cb50dacd942,
title = "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 associated with baseline and exercise-induced changes ( increment ) in insulin sensitivity index (S-i) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on S-i. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline S-i and increment S-i, 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 increment S-i further strengthens the relevance of calcium signalling in EET mediated S-i response.",
keywords = "PLASMA TRIGLYCERIDE RESPONSE, STIMULATED GLUCOSE-UPTAKE, INTERACTING PROTEIN 120B, MUSCLE FIBER-TYPE, SKELETAL-MUSCLE, GENE-EXPRESSION, RESISTANCE, INTERVENTION, IQCJ-SCHIP1, PREDICTORS",
author = "L.Y. Takeshita and P.K. Davidsen and J.M. Herbert and P. Antczak and M.K.C. Hesselink and P. Schrauwen and S.J. Weisnagel and J.M. Robbins and R.E. Gerszten and S. Ghosh and M.A. Sarzynski and C. Bouchard and F. Falciani",
note = "Funding Information: We thank Drs. Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Jacques Gagnon, Treva Rice and the late Jack H. Wilmore for contributions to the planning, data collection, and conduct of the HERITAGE project, and for the data management of the IVGTT. Special thanks are also given to Richard S. Bergman from the Cedars-Sinai Medical Centre for his expertise in the analyses of the IVGTT data. This research was partially funded by National Heart, Lung, and Blood Institute Grants HL-45670, HL-47317, HL-47321, HL-47323, and HL-47327, all in support of the HERITAGE Family Study). L.Y. Takeshita has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under the TransBioLine project with grant agreement No. 821283. This Joint Undertaking receives support from the European Union{\textquoteright}s Horizon 2020 research and innovation programme and EFPIA. This communication reflects the author{\textquoteright}s view and neither IMI nor the European Union or EFPIA are responsible for any use that may be made of the information contained therein. P. K. Davidsen was supported by a PhD studentship funded by the Birmingham MRC-ARUK Centre for Musculoskeletal Ageing Research. C. Bouchard is partially funded by the John W. Barton Sr. Chair in Genetics and Nutrition. Z. S. Ghosh and C. Bouchard are partially supported by the National Institute of General Medical Sciences (NIGMS)-funded COBRE Grant 8-P30-GM-118430-01. S. Ghosh is supported in part by NIGMS Grant 2-U54-GM-104940, which funds the Louisiana Clinical and Translational Science Center and by the National Medical Research Council, Ministry of Health, Singapore (WBS R913200076263). M. A. Sarzynski is partially supported by NHLBI Grant R01HL146462 and NIGMS Grant P20GM103499, which funds the South Carolina IDeA Network of Biomedical Research Excellence. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "2",
doi = "10.1038/s41598-021-98792-1",
language = "English",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}