1. Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training
- Author
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Louise Y. Takeshita, Jeremy M. Robbins, Mark A. Sarzynski, John Herbert, Claude Bouchard, Francesco Falciani, S. John Weisnagel, Philipp Antczak, Patrick Schrauwen, Matthijs K. C. Hesselink, Peter K. Davidsen, Robert E. Gerszten, Sujoy Ghosh, Nutrition and Movement Sciences, and RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health
- Subjects
Male ,Candidate gene ,Physiology ,MUSCLE FIBER-TYPE ,Transcriptome ,0302 clinical medicine ,INTERACTING PROTEIN 120B ,PLASMA TRIGLYCERIDE RESPONSE ,PREDICTORS ,Calcium signaling ,GENE-EXPRESSION ,0303 health sciences ,Multidisciplinary ,MEF2 Transcription Factors ,Middle Aged ,Phenotype ,Gene expression profiling ,Healthy Volunteers ,3. Good health ,Endurance Training ,Medicine ,SKELETAL-MUSCLE ,Female ,Chemokines ,INTERVENTION ,Adult ,Bioinformatics ,Science ,Genomics ,Computational biology ,Biology ,Article ,Young Adult ,03 medical and health sciences ,IQCJ-SCHIP1 ,Endurance training ,Genetics ,Humans ,Calcium Signaling ,Transcription factor ,Gene knockout ,STIMULATED GLUCOSE-UPTAKE ,030304 developmental biology ,Genetic Variation ,Physical Endurance ,Insulin Resistance ,030217 neurology & neurosurgery ,RESISTANCE ,Genome-Wide Association Study - 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.
- Published
- 2021