Gene and microRNA expression responses to exercise; relationship with insulin sensitivity

Carrie S. McLean, Clinton Mielke, Jeanine M. Cordova, Paul R. Langlais, Benjamin Bowen, Danielle Miranda, Dawn K. Coletta, Lawrence J. Mandarino

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Background: Healthy individuals on the lower end of the insulin sensitivity spectrum also have a reduced gene expression response to exercise for specific genes. The goal of this study was to determine the relationship between insulin sensitivity and exercise-induced gene expression in an unbiased, global manner. Methods and Findings: Euglycemic clamps were used to measure insulin sensitivity and muscle biopsies were done at rest and 30 minutes after a single acute exercise bout in 14 healthy participants. Changes in mRNA expression were assessed using microarrays, and miRNA analysis was performed in a subset of 6 of the participants using sequencing techniques. Following exercise, 215 mRNAs were changed at the probe level (Bonferroni-corrected P<0.00000115). Pathway and Gene Ontology analysis showed enrichment in MAP kinase signaling, transcriptional regulation and DNA binding. Changes in several transcription factor mRNAs were correlated with insulin sensitivity, including MYC, r=0.71; SNF1LK, r=0.69; and ATF3, r= 0.61 (5 corrected for false discovery rate). Enrichment in the 5′-UTRs of exercise-responsive genes suggested regulation by common transcription factors, especially EGR1. miRNA species of interest that changed after exercise included miR-378, which is located in an intron of the PPARGC1B gene. Conclusions: These results indicate that transcription factor gene expression responses to exercise depend highly on insulin sensitivity in healthy people. The overall pattern suggests a coordinated cycle by which exercise and insulin sensitivity regulate gene expression in muscle.

Original languageEnglish (US)
Article numbere0127089
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 18 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    McLean, C. S., Mielke, C., Cordova, J. M., Langlais, P. R., Bowen, B., Miranda, D., Coletta, D. K., & Mandarino, L. J. (2015). Gene and microRNA expression responses to exercise; relationship with insulin sensitivity. PloS one, 10(5), [e0127089]. https://doi.org/10.1371/journal.pone.0127089