Altered Transcription Factor Expression Responses to Exercise in Insulin Resistance
De Filippis, E.A.
AffiliationDivision of Endocrinology, Department of Medicine, University of Arizona
Center for Disparities in Diabetes, Obesity and Metabolism, University of Arizona Health Sciences
MetadataShow full item record
PublisherFrontiers Media S.A.
CitationZapata-Bustos, R., Finlayson, J., Langlais, P. R., Coletta, D. K., Luo, M., Grandjean, D., De Filippis, E. A., & Mandarino, L. (2021). Altered Transcription Factor Expression Responses to Exercise in Insulin Resistance. Frontiers in Physiology, 12.
JournalFrontiers in Physiology
RightsCopyright © 2021 Zapata-Bustos, Finlayson, Langlais, Coletta, Luo, Grandjean, De Filippis and Mandarino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractPurpose: Insulin resistant muscle is resistant to gene expression changes induced by acute exercise. This study was undertaken to identify transcription factors that differentially respond to exercise in insulin resistance. Candidate transcription factors were identified from analysis of 5′-untranslated regions (5′-UTRs) of exercise responsive genes and from analysis of the 5′-UTRs of genes coding for proteins that differ in abundance in insulin resistance. Research Design and Methods: Twenty participants took part in this study. Insulin sensitivity was assessed by an euglycemic clamp. Participants were matched for aerobic capacity and performed a single 48 min bout of exercise with sets at 70 and 90% of maximum heart rate. Muscle biopsies were obtained at resting conditions, 30 min and 24 h after exercise. Global proteomics analysis identified differentially abundant proteins in muscle. The 5′-UTRs of genes coding for significant proteins were subjected to transcription factor enrichment analysis to identify candidate transcription factors. Q-rt-PCR to determine expression of candidate transcription factors was performed on RNA from resting and post-exercise muscle biopsies; immunoblots quantified protein abundance. Results: Proteins involved in mitochondrial function, protein targeting and translation, and metabolism were among those significantly different between lean and obese groups. Transcription factor enrichment analysis of genes coding for these proteins revealed new candidate transcription factors to be evaluated along the previously identified factors. Q-rt-PCR analysis of RNA and immunoblot analysis from pre- and post-exercise muscle biopsies revealed several transcription and growth factors that had altered responses to exercise in insulin resistant participants. A significant increase (EGR3 and CTGF) and decrease (RELA and ATF2) in the mRNA expression of transcription and growth factors was found after exercise in the lean group, but not in the obese participants. Conclusions: These results confirm findings of an association between insulin sensitivity and transcription factor mRNA response to exercise and show that obesity also may be a sufficient prerequisite for exercise resistance. Analysis of the muscle proteome together with determination of effects of exercise on expression of transcription factors suggests that abnormal responses of transcription factors to exercise may be responsible for differences in protein abundances in insulin resistant muscle. © Copyright © 2021 Zapata-Bustos, Finlayson, Langlais, Coletta, Luo, Grandjean, De Filippis and Mandarino.
NoteOpen access journal
VersionFinal published version
Except where otherwise noted, this item's license is described as Copyright © 2021 Zapata-Bustos, Finlayson, Langlais, Coletta, Luo, Grandjean, De Filippis and Mandarino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).