Takeshita, Louise Y, Davidsen, Peter K, Herbert, John M, Antczak, Philipp 
ORCID: 0000-0001-9600-7757, Hesselink, Matthijs KC, Schrauwen, Patrick, Weisnagel, S John, Robbins, Jeremy M, Gerszten, Robert E, Ghosh, Sujoy et al (show 3 more authors)
(2021)
Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training.
SCIENTIFIC REPORTS, 11 (1).
23314-.
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 (S<sub>i</sub>) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on S<sub>i</sub>. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline S<sub>i</sub> and ∆S<sub>i</sub>, 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 ∆S<sub>i</sub> further strengthens the relevance of calcium signalling in EET mediated S<sub>i</sub> response.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Adult, Calcium Signaling, Chemokines, Endurance Training, Female, Genetic Variation, Genome-Wide Association Study, Healthy Volunteers, Humans, Insulin Resistance, MEF2 Transcription Factors, Male, Middle Aged, Physical Endurance, Transcriptome, Young Adult |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Jan 2022 11:22 |
| Last Modified: | 18 Jan 2023 21:15 |
| DOI: | 10.1038/s41598-021-98792-1 |
| Open Access URL: | https://doi.org/10.1038/s41598-021-98792-1 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3147105 |
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