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

L.Y. Takeshita, P.K. Davidsen, J.M. Herbert, P. Antczak, M.K.C. Hesselink, P. Schrauwen, S.J. Weisnagel, J.M. Robbins, R.E. Gerszten, S. Ghosh, M.A. Sarzynski, C. Bouchard, F. Falciani*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Article number23314
Number of pages14
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 2 Dec 2021

Keywords

  • PLASMA TRIGLYCERIDE RESPONSE
  • STIMULATED GLUCOSE-UPTAKE
  • INTERACTING PROTEIN 120B
  • MUSCLE FIBER-TYPE
  • SKELETAL-MUSCLE
  • GENE-EXPRESSION
  • RESISTANCE
  • INTERVENTION
  • IQCJ-SCHIP1
  • PREDICTORS

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