Skeletal muscle gene expression changes with exercise mode, duration and intensity: STRRIDE study
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ABSTRACT: Skeletal muscle adapts to exercise training of various modes, intensities and durations with a programmed gene expression response. This study dissects the independent and combined effects of exercise mode, intensity and duration to identify which exercise has the most positive effects on skeletal muscle health. Full details on exercise groups can be found in: Kraus et al Med Sci Sports Exerc. 2001 Oct;33(10):1774-84 and Bateman et al Am J Cardiol. 2011 Sep 15;108(6):838-44. This study uses a middle aged group of subjects that have 3+ markers of metabolic syndrome. One group remains an inactive control, while 5 groups undergo 9 mo supervised exercise training. Exercise groups are as follows: Inactive control (group B); Mild aerobic exercise - low amount/mod intensity (group A); Moderate aerobic exercise - low amt/vig intensity (group D); High aerobic exercise - high amt/vig intensity (group C); resistance training only (group F); and mod aerobic + resistance training (group E). Each group has 10 subjects (5 men and 5 women), however 3 subjects failed array QC, leaving 8 subjects in group E and 9 subjects in group F. Data were all analyzed pre to post training in a RM ANCOVA, covaried for age and sex or regression to determine genotype/phenotype interactions.
Project description:Maximal aerobic exercise capacity (V̇O2max) is one of the strongest predictors of morbidity and mortality. Aerobic exercise training can increase V̇O2max, but inter-individual variability is marked and unexplained physiologically. The mechanisms underlying this variability have major clinical implications for extending human healthspan. Here, we report the first comprehensive, RNA-seq study of circulating transcriptome signatures related to ΔV̇O2max. We used RNA-seq to characterize transcriptomic predictors of ΔV̇O2max in healthy women who completed a 16-week, randomized controlled trial comparing higher vs. lower aerobic exercise training volume and intensity (four training groups, fully crossed). We found striking baseline gene expression differences in subjects who responded to aerobic exercise training with robust (R) vs. little/no (NR) ΔV̇O2max.
Project description:Microarray analysis was performed with RNA isolated from vastus lateralis muscle biopsies of lean/overweight subjects following 18 days of aerobic exercise training. Samples from lean active individuals were also included. Exercise training led to robust changes in trained muscle. The lean active group profile was distinct from the pre-exercise samples. These results help define the molecular changes associated with aerobic training and contrast with an active phenotype.
Project description:STRRIDE is an exercise intervention study of different doses and intensities in overweight women and men with the metabolic syndrome. We profiled biopsies from 3 female and 3 male STRRIDE subjects in the “high” exercise group (2,200 kCal/wk). Muscle biopsies were profiled at entry (0h), and after 9 months of aerobic training (24 hrs post-last bout, 96 hrs post last bout, and 336h (14 days) de-training). Included also are pilot expression data from 3 male subjects. Keywords: other
Project description:STRRIDE is an exercise intervention study of different doses and intensities in overweight women and men with the metabolic syndrome. We profiled biopsies from 3 female and 3 male STRRIDE subjects in the âhighâ exercise group (2,200 kCal/wk). Muscle biopsies were profiled at entry (0h), and after 9 months of aerobic training (24 hrs post-last bout, 96 hrs post last bout, and 336h (14 days) de-training). Included also are pilot expression data from 3 male subjects.<br><br>Note that files GSM19162.txt and GSM20659.txt as downloaded from GEO are identical.
Project description:The aim of this work was to produce a reproducible molecular signature of human muscle responses to resistance training and examine how such a profile relates to new and established exercise adaptation gene networks. Subjects were recruited from an age range of 18 to 75 y. Before beginning the study all subjects were screened using a medical questionnaire, physical examination and resting ECG with exclusions for overt muscle wasting (>2 SD below age norms)[85], metabolic, respiratory/cardiovascular disorders or other major contraindications to a healthy status. All subjects had normal blood chemistry and were normotensive (BP <140/90). All subjects performed routine activities of daily living and recreation but did not participate in moderate to high intensity aerobic exercise and none had participated in RET in the last 24 months. Body composition was measured at screening and following RET by dual energy X-ray absorptiometry (DEXA) (Lunar Prodigy II, GE Medical Systems). Subject positioning on the DEXA bed was optimized to allow the region of interest (ROI) body compartments to be analyzed separately. The upper leg ROI was selected as the area inferior to the lowest visible point of the coccyx to the mid-point of the patella. The dataset comprises 44 pre-exercise and 44 post-exercise samples. In addition there is a baseline sample NB021_pre-training (D13_NB021F). Therefore there are 89 samples in total. (Note: Singleton baseline sample NB021_pre-training was normalized only using all baseline samples.) Derby dataset.
Project description:Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogeninâs role in adult skeletal muscle is unclear. We sought to determine myogeninâs function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we monitored blood glucose and lactate levels and performed histochemical analysis on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle. We used microarrays to detail the global program of gene expression underlying enhanced exercise endurance associated with myog-deletion and long-term exercise training. Mouse gastrocnemius muscles were selected after 6 months of myog-deletion and exercise training for RNA extraction and hybridization on Affymetrix microarrays. We chose 3 wild type and 3 myog-deleted mice that best represented the average of each larger group that was tested during our mouse exercise studies.
Project description:The study has been described in the following paper: Gianni Parise, Stuart M. Phillips, Jan J. Kaczor and Mark A. Tarnopolsky (2005). Antioxidant enzyme activity is up-regulated after unilateral resistance exercise training in older adults. Free Radical Biology and Medicine, Volume 39, Issue 2, 15 July 2005, Pages 289-295 We cite the following three paragraphs from this paper: "MATERIALS AND METHODS Subjects Twelve men (71.2 ± 6.5 y) volunteered to participate in a 12 week uni-lateral leg resistance training program (Table 1). All subjects underwent a thorough screening process before being admitted into the study. Subjects were first screened by telephone, and were then subject to a medical evaluation. Consent from their family physician was required, and then all potential subjects underwent a resting electrocardiogram, and a sub-maximal graded exercise test on a bicycle ergometer witih a 12-lead ECG. Exclusion criteria included: evidence of coronary hear disease; congestive heart failure; uncontrolled hypertension; chronic obstructive pulmonary disease; diabetes mellitus; renal failure; major orthopaedic disability; and smoking. None of the subjects had ever participated in a structured exercise program. After subjects were advised of the benefits and risks of participation, subjects gave their written informed consent. The study was approved by the McMaster University and Hamilton Health Sciences Research Ethics Board and conferred to the principles of the declaration of Helsinki. Exercise Training Resistance training was performed three times weekly on non-consecutive days (Monday, Wednesday, and Friday) for 12 weeks, under strict supervision. Prior to and after each training session subjects were required to perform passive stretching. Resistance exercise for each session consisted of 3 sets of 10 repetitions for each of leg press and leg extension. Training progressed from one set of each exercise at 50% of the initial 1 repetition maximum (1RM) to 3 sets at 80% of 1RM over the training period. Training logs were kept to record the volume and intensity of each session. The 1RM was re-evaluated every 2 weeks, and the training load was adjusted accordingly. All exercises were performed on universal strength training equipment (Universal Gym Equipment, Inc., Cedar Rapids, Iowa). Muscle Biopsy A muscle biopsy was taken from the vastus lateralis muscle of both legs before as well as after the training period, 20 cm proximal to the knee joint using a modified Bergström needle (5 mm diameter) with suction modification. The biopsy specimen was dissected of fat and connective tissue and immediately frozen in liquid nitrogen. All samples were stored at -80 °C for subsequent analysis. All subjects were required to abstain from strenuous physical activity for 48 hours prior to the testing session. The non-trained leg performed an acute bout of exercise at the same relative intensity of the training leg to allow for the determination of the effect of training and the effect of acute resistance exercise." Additional Notes: 1) The samples of 8 out 12 were used in the gene expression study. 2) The 2 factors in this study are: 2.1) Leg - Left or Right 2.2) Training - Baseline: samples taken on each leg before exercise - Resistance Training: one of the legs was subject to resistance training followed by acute exercise - Acute Exercise: the other leg had only the acute exercise 3) The baseline samples will be used for right versus left leg comparison to see variance between legs for human experimentation technical issues. The samples from Resistance or Acute Exercise will be compared to corresponding baseline samples to evaluate the effect of both exercise programs on gene expression.
Project description:The overall objective of the heritage project is to study the role of the genotype in cardiovascular,metabolic and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in several cardiovascular disease and diabetes risk factors. The study cohort in this analysis consists of 473 Caucasian subjects (230 male and 243 female) from 99 nuclear families who completed M-bM-^IM-%58 of the prescribed 60 exercise-training sessions.The phenotypic expression of each individualM-bM-^@M-^Ys genotype is assessed under two well-defined environmental conditions, the pre- and post-training conditions. Here we have made the pre-training data available as used in the article Phillips BE, Williams JP, Gustafsson T, Bouchard C, Rankinen T, et al. (2013) Molecular Networks of Human Muscle Adaptation to Exercise and Age. PLoS Genet 9(3): e1003389. doi:10.1371/journal.pgen.1003389 52 U133+2 profiles (17M-bM-^@M-^S63 yr) generated from pre-exercise muscle biopsy samples from the HERITAGE Family Study. Heritage_pre dataset.
Project description:In our study, we investigated for contractile activity-specific changes in the transcriptome in untrained and trained (after an aerobic training programme) human skeletal muscle. The second goal was to examine effect of aerobic training on gene expression in muscle at baseline (after long term training). Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (baseline condition, 48 h after exercise), 1 and 4 h after the one-legged exercise from m. vastus lateralis of either leg. Comparison of gene expression in exercised leg with that in non-exercised [control] leg allowed us to identify contractile activity-specific genes in both untrained and trained skeletal muscle, i.e., genes that play a key role in adapting to acute exercise, regardless of the level of fitness. RNA-sequencing (84 samples in total; ~47 million reads/sample) was performed by NextSeq 500 and HiSeq 2500 (Illumina). Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in the incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. Contractile activity-specific changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, transcriptome responses specific for contractile activity in trained muscle substantially decreased relative to those in untrained muscle. We found out that adaptation of skeletal muscle to regular exercise is associated not only with a transient change in the transcriptome after each stress (acute exercise), but also with a marked change in baseline expression of many genes after repeated stress (e.g., long term training).
Project description:Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are exercise resistant, and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise resistant phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFβ signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.