Abstract
PurposeInsulin 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 MethodsTwenty 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.ResultsProteins 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.ConclusionsThese 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.
Highlights
The results of many studies reveal a variety of differences between skeletal muscle from insulin sensitive and insulin resistant individuals
Our earlier studies showed a clear relationship between insulin resistance and lack of acute gene expression responses to insulin, it is unclear whether obesity itself is associated with the impaired gene expression response to a single bout of exercise
In addition to transcription factors that were identified previously as potential candidates for explaining altered gene expression changes in response to exercise in insulin resistance, we reasoned that differences in protein abundance in insulin sensitive and insulin resistant muscle might be explained by exercise resistance
Summary
The results of many studies reveal a variety of differences between skeletal muscle from insulin sensitive and insulin resistant individuals. One intriguing difference that has received attention is the observation that transcriptional responses to acute exercise are related to insulin sensitivity but are independent of obesity. This concept derives from studies in which participants matched for body composition but differing in insulin sensitivity were found to have different gene expression responses to a single exercise bout, suggesting that insulin resistant muscle is “exercise resistant” (De Filippis et al, 2008; McLean et al, 2015). Our earlier studies showed a clear relationship between insulin resistance and lack of acute gene expression responses to insulin, it is unclear whether obesity itself is associated with the impaired gene expression response to a single bout of exercise
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
