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.

Details

Title
Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
Author
Takeshita, Louise Y 1 ; Davidsen, Peter K 1 ; Herbert, John M 1 ; Antczak Philipp 2 ; Hesselink, Matthijs K, C 3 ; Schrauwen, Patrick 3 ; John, Weisnagel S 4 ; Robbins, Jeremy M 5 ; Gerszten, Robert E 5 ; Ghosh Sujoy 6 ; Sarzynski Mark A 7 ; Bouchard, Claude 8 ; Falciani, Francesco 1 

 University of Liverpool, Institute of Systems, Molecular and Integrative Biology, Liverpool, UK (GRID:grid.10025.36) (ISNI:0000 0004 1936 8470) 
 University of Liverpool, Institute of Systems, Molecular and Integrative Biology, Liverpool, UK (GRID:grid.10025.36) (ISNI:0000 0004 1936 8470); University Hospital Cologne, Center for Molecular Medicine Cologne, Cologne, Germany (GRID:grid.411097.a) (ISNI:0000 0000 8852 305X) 
 Maastricht University Centre, Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
 Université Laval, Diabetes Research Unit, Endocrinology and Nephrology Axis, CRCHU de Québec, Québec City, Canada (GRID:grid.23856.3a) (ISNI:0000 0004 1936 8390) 
 Beth Israel Deaconess Medical Center, Division of Cardiovascular Medicine, and Cardiovascular Research Center, Boston, USA (GRID:grid.239395.7) (ISNI:0000 0000 9011 8547) 
 Duke-NUS Medical School, Centre for Computational Biology and Program in Cardiovascular and Metabolic Disorders, Singapore, Singapore (GRID:grid.428397.3) (ISNI:0000 0004 0385 0924) 
 University of South Carolina, Department of Exercise Science, Arnold School of Public Health, Columbia, USA (GRID:grid.254567.7) (ISNI:0000 0000 9075 106X) 
 Pennington Biomedical Research Center, Human Genomics Laboratory, Baton Rouge, USA (GRID:grid.250514.7) (ISNI:0000 0001 2159 6024) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2605422453
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.