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

22 Citations (Scopus)

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
Externally publishedYes

Fingerprint

MicroRNAs
microRNA
insulin resistance
Insulin Resistance
Gene expression
exercise
Genes
Exercise
Insulin
Gene Expression
genes
gene expression
Messenger RNA
Muscle
transcription factors
Early Growth Response Protein 1
Transcription Factors
Biopsy
5' Untranslated Regions
Clamping devices

ASJC Scopus subject areas

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

Cite this

McLean, C. S., Mielke, C., Cordova, J. M., Langlais, P. R., Bowen, B., Miranda, D., ... 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

Gene and microRNA expression responses to exercise; relationship with insulin sensitivity. / McLean, Carrie S.; Mielke, Clinton; Cordova, Jeanine M.; Langlais, Paul R.; Bowen, Benjamin; Miranda, Danielle; Coletta, Dawn K.; Mandarino, Lawrence J.

In: PloS one, Vol. 10, No. 5, e0127089, 18.05.2015.

Research output: Contribution to journalArticle

McLean, Carrie S. ; Mielke, Clinton ; Cordova, Jeanine M. ; Langlais, Paul R. ; Bowen, Benjamin ; Miranda, Danielle ; Coletta, Dawn K. ; Mandarino, Lawrence J. / Gene and microRNA expression responses to exercise; relationship with insulin sensitivity. In: PloS one. 2015 ; Vol. 10, No. 5.
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