Untrained Muscle Research Articles

The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles.

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO2max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO2max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.

Training-Induced Increase in V·O2max and Critical Power, and Acceleration of V·O2 on-Kinetics Result from Attenuated Pi Increase Caused by Elevated OXPHOS Activity.

Computer simulations using a dynamic model of the skeletal muscle bioenergetic system, involving the Pi-double-threshold mechanism of muscle fatigue, demonstrate that the training-induced increase in V·O2max, increase in critical power (CP) and acceleration of primary phase II of the V·O2 on kinetics (decrease in t0.63) is caused by elevated OXPHOS activity acting through a decrease in and slowing of the Pi (inorganic phosphate) rise during the rest-to-work transition. This change leads to attenuation of the reaching by Pi of Pipeak, peak Pi at which exercise is terminated because of fatigue. The delayed (in time and in relation to V·O2 increase) Pi rise for a given power output (PO) in trained muscle causes Pi to reach Pipeak (in very heavy exercise) after a longer time and at a higher V·O2; thus, exercise duration is lengthened, and V·O2max is elevated compared to untrained muscle. The diminished Pi increase during exercise with a given PO can cause Pi to stabilize at a steady state less than Pipeak, and exercise can continue potentially ad infinitum (heavy exercise), instead of rising unceasingly and ultimately reaching Pipeak and causing exercise termination (very heavy exercise). This outcome means that CP rises, as the given PO is now less than, and not greater than CP. Finally, the diminished Pi increase (and other metabolite changes) results in, at a given PO (moderate exercise), the steady state of fluxes (including V·O2) and metabolites being reached faster; thus, t0.63 is shortened. This effect of elevated OXPHOS activity is possibly somewhat diminished by the training-induced decrease in Pipeak.

Effects of Upper Body Exercise Training on Aerobic Fitness and Performance in Healthy People: A Systematic Review

Purpose: This systematic review aimed to evaluate the effects of upper body endurance training (UBET) on oxygen uptake (VO2) in healthy persons and derive evidence-based recommendations to improve upper body fitness and performance. Methods: Databases were systematically searched in accordance with PRISMA guidelines until 1 February 2023. Eligibility criteria included healthy male and female adults and older adults who underwent an UBET intervention. Outcomes of interest included physical fitness (VO2peak and/ or VO2 submax) and transfer effects (i.e., effects from trained (VO2peak ARM) to untrained (VO2peak LEG) musculature). Results: The search identified 8293 records, out of which 27 studies reporting on 29 interventions met our eligibility criteria. The average duration of interventions was 6.8 ± 2.6 weeks with 3.2 ± 0.8 training sessions per week. For 21 of 29 interventions, significant increases in VO2peak ARM were reported following UBET (+16.4% ± 8.3%). Three of the nine studies that analyzed transfer effects of untrained legs after upper body training exhibited significant increases in VO2peak LEG (+9.3% ± 2.6%). Conclusions: This review showed that UBET is a beneficial and useful training modality to increase the oxygen utilization in the upper body. Although UBET is an uncommon form of endurance training in healthy individuals, transfer effects to the untrained muscles can be observed in isolated cases only, rendering transfer effects in UBET inconclusive. Further research should focus on the peripheral changes in muscle morphology of the trained muscles and central changes in cardiovascular function as well as when transfer effects can occur after UBET in healthy people.

Skeletal muscle biochemical origin of exercise intensity domains and their relation to whole-body V̇O2 kinetics.

This article presents the biochemical intra-skeletal-muscle basis of exercise intensity domains: moderate (M), heavy (H), very heavy (VH) and severe (S). Threshold origins are mediated by a ‘Pi double-threshold’ mechanism of muscle fatigue, which assumes (1) additional ATP usage, underlying muscle V̇O2 and metabolite slow components, is initiated when inorganic phosphate (Pi) exceeds a critical value (Picrit); (2) exercise is terminated because of fatigue, when Pi reaches a peak value (Pipeak); and (3) the Pi increase and additional ATP usage increase mutually stimulate each other forming a positive feedback. M/H and H/VH borders are defined by Pi on-kinetics in relation to Picrit and Pipeak. The values of the ATP usage activity, proportional to power output (PO), for the M/H, H/VH and VH/S borders are lowest in untrained muscle and highest in well-trained muscle. The metabolic range between the M/H and H/VH border (or ‘H space’) decreases with muscle training, while the difference between the H/VH and VH/S border (or ‘VH space’) is only weakly dependent on training status. The absolute magnitude of the muscle V̇O2 slow-component, absent in M exercise, rises gradually with PO to a maximal value in H exercise, and then decreases with PO in VH and S exercise. Simulations of untrained, physically active and well-trained muscle demonstrate that the muscle M/H border need not be identical to the whole-body M/H border determined from pulmonary V̇O2 on-kinetics and blood lactate, while suggesting that the biochemical origins of the H/VH border reside within skeletal muscle and correspond to whole-body critical power.

Recurrent training rejuvenates and enhances transcriptome and methylome responses in young and older human muscle

AbstractBackgroundThe interaction between the muscle methylome and transcriptome is understudied during ageing and periods of resistance training in young, but especially older adults. More information is needed on the role of retained methylome training adaptations in muscle memory to understand muscle phenotypical and molecular restoration after inactivity or disuse.MethodsWe measured CpG methylation (microarray) and RNA expression (RNA sequencing) in young (n = 5; age = 22 ± 2 years) and older (n = 6; age = 65 ± 5 years) vastus lateralis muscle samples, taken at baseline, after 12 weeks of resistance training, after training interruption (2 weeks of leg immobilization in young men, 12 weeks of detraining in older men) and after 12 weeks of retraining to identify muscle memory‐related adaptations and rejuvenating effects of training.ResultsWe report that of the 427 differentially expressed genes with advanced age (FDR < 0.1), 71% contained differentially methylated (dm)CpGs in older versus young muscle (FDR < 0.1, M‐value difference >0.4). The more dmCpGs within a gene, the clearer the inverse methylation–expression relationship. Around 73% of the age‐related dmCpGs approached younger methylation levels when older muscle was trained for 12 weeks. A second resistance training period after training cessation increased the number of hypomethylated CpGs and upregulated genes in both young and older muscle. We found indication for an epi‐memory within pro‐proliferating AMOTL1 in young muscle and mechanosensing‐related VCL in older muscle. For the first time, we integrate muscle methylome and transcriptome data in relation to both ageing and training‐induced/inactivity‐induced responses and identify focal adhesion as an important pathway herein.ConclusionsThis preliminary evidence indicates that previously trained muscle is more responsive to training than untrained muscle at methylome and transcriptome level and recurrent resistance training can partially restore ageing‐induced methylome alterations.

Mechanism and Theories for Delayed Onset of Muscle Soreness in Athletes

The sensation of tenderness and tightness over the muscle, post eccentric exercise is called Delayed Onset of Muscle Soreness (DOMS). It is not an acute pain. Post exercise the soreness will develop within 24-72 hours of duration, slowly the soreness will reduce by 5-7 days post exercise. Initially Theodre Hough, mentioned soreness will develop when an untrained muscle does a contraction opposite to the strong spring. The aim of this review article is to find out the various mechanisms and theories for Delayed Onset of Muscle Soreness development. A direct search of journals was conducted to identify the potential articles. Online search engines such as PubMed, Google Scholar, MEDLINE, and Physiotherapy Evidence-based Database (PEDro) were searched. Based on the available research studies, Delayed onset of muscle soreness developmental mechanism was understood. Literature search helped to understand the various theories on development of DOMS and physiology behind the soreness. Still more articles and research must emerge to provide the clear evidence on theories on Delayed Onset of Muscle Soreness.

Low force exercise training using muscle stimulation adapts physiologic phenotype in people with Spinal Cord Injury

Physical activity, even in short bursts, is critical to maintain human skeletal muscle. Low physical activity levels are associated with poor health, chronic non‐communicable diseases (NCDs), and impaired cognition in people with intact nervous systems as they age. Exercise as a form of medicine increases physical activity levels, attenuates the development of NCDs, and improves cognitive capacity. Because people with spinal cord injury (SCI) cannot volitionally activate their paralyzed muscles, the musculoskeletal system deteriorates with an increased risk for NCDs and cognitive decline as they age. High force electrically induced exercise is risky; therefore, a safe low‐force alternative is needed. Whether training using a low‐force electrically induced exercise can influence muscle and systemic health markers in people with SCI is unknown.PurposeTo determine if low‐force electrically induced exercise changes the phenotype and metabolic health of paralyzed skeletal muscle in people with SCI.Methods10 people with complete SCI completed electrically induced exercise training using low‐force (3Hz) stimulation of the quadriceps. Participants targeted at least 5 exercise training sessions per week. A muscle fatigue test and fasting venous blood draw, measuring CRP, insulin, leptin, BDNF, myostatin, and PTH, were performed before and after training. Muscle biopsies were obtained from a trained and untrained vastus lateralis. Gene expression was measured using the Affymetrix HTA 2.0 array from the trained and untrained muscle samples. All participants provided written consent approved by the University of Iowa Institutional Review Board in compliance with the Declaration of Helsinki.ResultsParticipants were compliant completing ~119±19% of the training sessions for ~7.2±1.2 months. There was a ~68% improvement in fatigue after of exercise training compared to baseline (p=0.002). There was a significant increase in the resting gene expression of slow‐twitch proteins MYH6(p=0.023), MYH7(p=0.034), and MYL3(p=0.022) compared to the untrained limb. Serum concentration of CRP, insulin, myostatin, and leptin were decreased by ~74% (p=0.089), ~179%(0.057), ~64%(p=0.096), and ~79%(p=0.021) after exercise training compared to baseline, respectively. Serum BDNF and PTH concentration were increased by ~70%(p=0.093) and ~78%(p=0.048) after exercise training, respectively.ConclusionsLow‐force electrically induced exercise training improved fatigability and phenotype of paralyzed muscle. Consistent with this change, the homeostatic gene expression of slow‐twitch proteins (MYH6, MYH7, and MYL3) were increased, but the transcription factors (PGC1a and MSTN) remained unchanged. Serum biomarkers (CRP, insulin, leptin, BDNF, myostatin and PTH) showed a consistent trend systemic metabolic health after training. Together, this study highlights the potential of low‐force electrically induced exercise to improve the health in people with chronic SCI, though the minimum duration of training required may be delayed compared to other exercises modalities.Support or Funding InformationResearch SupportThis study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HD084645, R01HD082109

Morphology and Anabolic Response of Skeletal Muscles Subjected to Eccentrically or Concentrically Biased Exercise.

Long-term eccentric exercise is known to promote muscle growth better than concentric exercise, but its acute effect on muscle is not well understood because of misinterpreted modeling and in situ and in vitro stretch protocols. Knowing if the initial bout of eccentric exercise promotes muscle growth and limits damage is critical to understanding the effect of this mode of exercise. To directly evaluate the immediate effects of eccentric and concentric exercises on untrained muscle when fiber strains were physiological and exercise doses were comparable. Controlled laboratory study. Laboratory. A total of 40 skeletally mature male Long-Evans rats (age = 16 weeks, mass = 452.1 ± 35.2 g) were randomly assigned to an eccentric exercise (downhill walking, n = 16), concentric exercise (uphill walking, n = 16), or control (no exercise, n = 8) group. Rats were exposed to a single 15-minute bout of eccentric or concentric exercise on a motorized treadmill and then were euthanized at 6 or 24 hours postexercise. We harvested the vastus lateralis muscle bilaterally. The percentage increase or decrease in protein abundance in exercised animals relative to that in unexercised control animals was evaluated as elevated phosphorylated p70S6k relative to total p70S6k. Fiber damage was quantified using immunoglobulin G permeability staining. One-way analysis of variance and post hoc Tukey tests were performed. Rats exposed to eccentric exercise and euthanized at 24 hours had higher percentage response protein synthesis rates than rats exposed to eccentric exercise and euthanized at 6 hours (P = .02) or to concentric exercise and euthanized at 6 (P = .03) or 24 (P = .03) hours. We assessed 9446 fibers for damage and found only 1 fiber was infiltrated (in the concentric exercise group euthanized at 6 hours). Furthermore, no between-groups differences in immunoglobulin G fluorescent intensity were detected (P = .94). Incorporating eccentric exercise is a simple, universally available therapeutic intervention for promoting muscle recovery. A single 15-minute dose of eccentric exercise to a novice muscle can better exert an anabolic effect than a comparable dose of concentric exercise, with very limited evidence of fiber damage.

Cross-training effect of chronic whole-body vibration exercise: a randomized controlled study

Purpose: To determine whether unilateral leg whole-body vibration (WBV) strength training induces strength gain in the untrained contralateral leg muscle. The secondary aim was to determine the potential role of spinal neurological mechanisms regarding the effect of WBV exercise on contralateral strength training.Materials and Methods: Forty-two young adult healthy volunteers were randomized into two groups: WBV exercise and Sham control. An isometric semi-squat exercise during WBV was applied regularly through 20 sessions. WBV training was applied to the right leg in the WBV group and the left leg was isolated from vibration. Sham WBV was applied to the right leg of participants in the Control group. Pre- and post-training isokinetic torque and reflex latency of both quadricepses were evaluated.Results: The increase in the strength of right (vibrated) knee extensors was 9.4 ± 10.7% in the WBV group (p = .001) and was 1.2 ± 6.6% in the Control group (p = .724). The left (non-vibrated) extensorsvibrated) knee extensors w4 ± 8.4% in the WBV group (p = .038), whereas it decreased by 1.4 ± 7.0% in the Control (p = .294). The strength gains were significant between the two groups. WBV induced the reflex response of the quadriceps muscle in the vibrated ipsilateral leg and also in the non-vibrated contralateral leg, though with a definite delay. The WBV-induced muscle reflex (WBV-IMR) latency was 22.5 ± 7.7 ms for the vibrated leg and 39.3 ± 14.6 ms for the non-vibrated leg.Conclusions: Chronic WBV training has an effect of the cross-transfer of strength to contralateral homologous muscles. The WBV-induced muscular reflex may have a role in the mechanism of cross-transfer strength.

Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury.

Exercise attenuates the development of chronic noncommunicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short- or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed by a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for metabolism (38 gene sets), cell cycle (36 gene sets), disease (27 gene sets), gene expression and transcription (22 gene sets), organelle biogenesis (4 gene sets), cellular response to stimuli (8 gene sets), immune system (8 gene sets), vesicle-mediated transport (4 gene sets), and transport of small molecules (3 gene sets). Specific gene expression included: oxidative catabolism of glucose including PDHB (P < 0.001), PDHX (P < 0.001), MPC1 (P < 0.009), and MPC2 (P < 0.007); Oxidative phosphorylation genes including SDHA (P < 0.006), SDHB (P < 0.001), NDUFB1 (P < 0.002), NDUFA2 (P < 0.001); transcription genes including PGC1α (P < 0.030) and PRKAB2 (P < 0.011); hypertrophy gene MSTN (P < 0.001); and the myokine generating FNDC5 gene (P < 0.008). Long-term electrically induced exercise demethylated the major transcription factor PGC1a. Taken together, these findings support that long-term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.

A secondary analysis of testosterone and electrically evoked resistance training versus testosterone only (TEREX-SCI) on untrained muscles after spinal cord injury: a pilot randomized clinical trial.

Study design:Secondary analysis of a clinical trialObjectives:To perform a secondary analysis on the effects of neuromuscular electrical stimulation resistance training (RT) combined with testosterone replacement therapy (TRT) compared to TRT on the untrained muscles after spinal cord injury (SCI).Setting:Medical research centerMethods:Twenty-two men with chronic motor complete SCI were randomized into TRT+RT group (n=11) or TRT group (n=11). Both groups received 16 weeks of TRT (2-6 mg/day) via testosterone patches. The TRT+RT group received twice-weekly progressive RT of the knee extensor muscles using electrical stimulation and ankle weights. Magnetic resonance images were captured to measure cross-sectional areas (CSAs) of trunk, glutei, and leg muscles.Results:Total and absolute gluteus maximus m. (14%, P= 0.003 and 16%, P= 0.001), gluteus medius m. (10%; P= 0.008 and 14%; P= 0.02) and total glutei m. (8%, P= 0.01 and 11%, P= 0.005) CSAs increased overtime for the TRT+RT group. Mean between group differences of 2.86 (95% CI:0.30, 5.4), 1.89 (95% CI:0.23, 3.58) and 5.27 (95% CI:0.90, 9.69) cm2 were noted for absolute gluteus maximus, total gluteus medius and total glutei CSAs, respectively (P< 0.05). Trunk muscle CSAs showed a trend towards an interaction between groups.Conclusion:RT combined with low-dose TRT results in significant hypertrophy compared to TRT only on the adjacent untrained glutei muscles. Trunk muscles may require direct stimulation to evoke hypertrophy. These exploratory findings may be of clinical relevance in the reduction of incidence and severity of pelvic pressure injuries.

Global Training Effects of Trained and Untrained Muscles With Youth Can be Maintained During 4 Weeks of Detraining.

Chaouachi, A, Ben Othman, A, Makhlouf, I, Young, JD, Granacher, U, and Behm, DG. Global training effects of trained and untrained muscles with youth can be maintained during 4 weeks of detraining. J Strength Cond Res 33(10): 2788-2800, 2019-Global (whole-body) effects of resistance training (i.e., cross-education) may be pervasive with children. Detraining induces less substantial deficits with children than adults. It was the objective of this study to investigate the global responses to 4 weeks of detraining after 8 weeks of unilateral leg press (LP) training in 10-13-year-old, pre-peak-height-velocity stage boys. Subjects were randomly separated into 2 unilateral resistance training groups (high load/low repetitions [HL-LR] and low load/high repetitions [LL-HR], and control group). Assessments at pre-training, post-training, and detraining included dominant and nondominant limbs, unilateral, 1 repetition maximum (1RM) and 60% 1RM LP, knee extension, knee flexion, elbow flexion, and handgrip maximal voluntary isometric contraction (MVIC), and countermovement jump (CMJ). All measures significantly increased from pre-test to detraining for both training programs, except for elbow flexion MVIC with increases only with HL-LR. All measures except CMJ and handgrip MVIC significantly decreased from post-test to detraining, except for elbow flexion MVIC with decreases only with HL-LR. The dominant trained limb experienced significantly greater LP improvements (pre- to detraining) and decrements (post- to detraining) with LP 1RM and 60% 1RM LP. In conclusion, youth HL-LR and LL-HR global training effects of trained and untrained limbs demonstrate similar benefits (pre- to detraining) and decrements (post- to detraining) with detraining. The findings emphasize that training any muscle group in a child can have positive global implications for improved strength and power that can persist over baseline measures for at least a month.

Effects of one-legged high-intensity interval training on insulin-mediated skeletal muscle glucose homeostasis in patients with type 2 diabetes.

To examine the effect of high-intensity interval training (HIIT) on glucose clearance rates in skeletal muscle and explore the mechanism within the muscle. Ten males with type 2 diabetes mellitus (T2DM) and ten matched healthy subjects performed 2weeks of one-legged HIIT (total of eight sessions, each comprised of 10×1minute ergometer bicycle exercise at >80% of maximal heart rate, interspersed with one min of rest). Insulin sensitivity was assessed by an isoglycaemic, hyperinsulinaemic clamp combined with arteriovenous leg balance technique of the trained (T) and the untrained (UT) leg and muscle biopsies of both legs. Insulin-stimulated glucose clearance in T legs was ~30% higher compared with UT legs in both groups due to increased blood flow in T vs UT legs and maintained glucose extraction. With each training session, muscle glycogen content decreased only in the training leg, and after the training, glycogen synthase and citrate synthase activities were higher in T vs UT legs. No major changes occurred in the expression of proteins in the insulin signalling cascade. Mitochondrial respiratory capacity was similar in T2DM and healthy subjects, and unchanged by HIIT. HIIT improves skeletal muscle insulin sensitivity. With HIIT, the skeletal muscle of patients with T2DM becomes just as insulin sensitive as untrained muscle in healthy subjects. The mechanism includes oscillations in muscle glycogen stores and a maintained ability to extract glucose from the blood in the face of increased blood flow in the trained leg.

Isometric resistance training increases strength and alters histopathology of dystrophin-deficient mouse skeletal muscle.

Mutation to the dystrophin gene causes skeletal muscle weakness in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD). Deliberation continues regarding implications of prescribing exercise for these patients. The purpose of this study was to determine whether isometric resistance exercise (~10 tetanic contractions/session) improves skeletal muscle strength and histopathology in the mdx mouse model of DMD. Three isometric training sessions increased in vivo isometric torque (22%) and contractility rates (54%) of anterior crural muscles of mdx mice. Mice expressing a BMD-causing missense mutated dystrophin on the mdx background showed comparable increases in torque (22%), while wild-type mice showed less change (11%). Increases in muscle function occurred within 1 h and peaked 3 days posttraining; however, the adaptation was lost after 7 days unless retrained. Six isometric training sessions over 4 wk caused increased isometric torque (28%) and contractility rates (22-28%), reduced fibrosis, as well as greater uniformity of fiber cross-sectional areas, fewer embryonic myosin heavy-chain-positive fibers, and more satellite cells in tibialis anterior muscle compared with the contralateral untrained muscle. Ex vivo functional analysis of isolated extensor digitorum longus (EDL) muscle from the trained hindlimb revealed greater absolute isometric force, lower passive stiffness, and a lower susceptibility to eccentric contraction-induced force loss compared with untrained EDL muscle. Overall, these data support the concept that exercise training in the form of isometric tetanic contractions can improve contractile function of dystrophin-deficient muscle, indicating a potential role for enhancing muscle strength in patients with DMD and BMD. NEW & NOTEWORTHY We focused on adaptive responses of dystrophin-deficient mouse skeletal muscle to isometric contraction training and report that in the absence of dystrophin (or in the presence of a mutated dystrophin), strength and muscle histopathology are improved. Results suggest that the strength gains are associated with fiber hypertrophy, reduced fibrosis, increased number of satellite cells, and blunted eccentric contraction-induced force loss in vitro. Importantly, there was no indication that the isometric exercise training was deleterious to dystrophin-deficient muscle.

PL-008 Adaptation of skeletal muscle to aerobic exercise: specific transcriptome response to acute exercise and training

Objective Variety of processes including circadian rhythm and systemic factors affect expression of many genes in skeletal muscle during a day. Therefore, post-exercise gene expression depends on many factors: contractile activity per seas well as circadian rhythm, nerve activity, concentration of different substances in blood, feeding and fasting. In our study, we investigated specific for contractile activity 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 in basal state.&#x0D; Methods 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 (basal state, 48 h after the previous exercise), 1 and 4 h after one-legged exercise from m. vastus lateralisof either leg. This approach allowed us to evaluate specific changes in the transcriptome associated with contractile activity. RNA­sequencing (84 samples in total; ~42 million reads/sample) was performed by HiSeq 2500 (Illumina).&#x0D; Results Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. After one-legged exercise, expression of many genes was changed in exercised muscle (~1500) as well as in non-exercised muscle (~400). Pronounced changes in gene expression in non-exercised muscle may be associated with many factors, including circadian rhythm (result of GO analysis).&#x0D; To examine transcriptome changes specific for contractile activity, the difference in gene expression between legs was examined. In untrained muscle, one-legged exercise changed expression of ~1200 genes specific for contractile activity at each time point. Despite the same relative intensity of one-legged exercise, transcriptomic response in trained muscle was markedly lower (~300 genes) compare to untrained.&#x0D; We observed a strong overlap between transcriptomic responses (~250 genes) and particularly between enriched transcription factor binding sites in promoters of these genes in untrained and trained muscles. These sets of genes and transcription factors play the key role in adaptation of muscle to contractile activity independently on the level of muscular fitness.&#x0D; Surprisingly, 2 months aerobic training changed the expression of more than 1500 genes in basal state. Noteworthy, these genes demonstrated a small overlap (~200 genes) with genes related to specific response to acute exercise. Moreover, these genes were associated with significantly different biological processes than genes related to specific response to acute exercise.&#x0D; Conclusions Specific for contractile activity changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, the specific transcriptome response to acute exercise become much less pronounced. A computational approach reveals common transcription factors important for adaptation of both untrained and trained muscle. We found out that adaptation of muscle to aerobic training associates not only with the transitory changes in gene expression after each exercise, but also with the marked changes in transcriptome in basal state.&#x0D; This work was supported by the Russian Science Foundation (14­15­00768).

Regulation of PPARGC1A gene expression in trained and untrained human skeletal muscle.

Promoter‐specific expression of the PPARGC1A gene in untrained and trained human skeletal muscle was investigated. Ten untrained males performed a one‐legged knee extension exercise (for 60 min) with the same relative intensity both before and after 8 weeks of cycling training. Samples from the m. vastus lateralis of each leg were taken before and after exercise. Postexercise PPARGC1A gene expression via the canonical promoter increased by ~100% (P < 0.05) in exercised and nonexercised untrained muscles, but did not change in either leg after training program. In untrained and trained exercised muscle, PPARGC1A gene expression via the alternative promoter increased by two orders of magnitude (P < 0.01). We found increases in postexercise content of dephosphorylated (activated) CRTC2, a coactivator of CREB1, in untrained exercised muscle and in expression of CREB1‐related genes in untrained and trained exercised muscle (P < 0.01–0.05); this may partially explain the increased expression of PPARGC1A via the alternative promoter. In addition, comparison of the regulatory regions of both promoters revealed unique conserved motifs in the alternative promoter that were associated with transcriptional repressors SNAI1 and HIC1. In conclusion, in untrained muscle, exercise‐induced expression of the PPARGC1A gene via the canonical promoter may be regulated by systemic factors, while in trained muscle the canonical promoter shows constitutive expression at rest and after exercise. Exercise‐induced expression of PPARGC1A via the alternative promoter relates to intramuscular factors and associates with activation of CRTC2‐CREB1. Apparently, expression via the alternative promoter is regulated by other transcription factors, particularly repressors.

Clinician perspectives on cross-education in stroke rehabilitation

Purpose: Cross-education is a neural phenomenon where strength of an untrained muscle improves after unilateral training of the opposite homologous muscle. It has been extensively studied in healthy populations and shows promise for post-stroke rehabilitation. The purpose of this study is to understand current post-stroke upper extremity rehabilitation practice; clinician’s perspectives on cross-education and; facilitators and barriers to implementation of a cross-education intervention.Materials and methods: This qualitative study used an interpretive description framework. Twenty-three occupational therapists and two physiotherapists who worked with individuals with stroke were interviewed. Digital audio files were transcribed and then line-by-line coding for units of information was conducted by two investigators. A third investigator, who was not present during the interviews, participated in category development.Results and conclusions: Cross-education is paradoxical yet promising was the primary theme. This theme was elucidated by three descriptive categories: (1) therapists worked in a forced-use paradigm; (2) there was gap in current practice for those with more severe impairments in arm function; and (3) cross-education used as an adjunct could be useful within current practice for specific patients. Therapists suggested that educational materials for clinicians, patients, and patient families would be essential to the success of cross-education to explain training the less affected limb. This study provides important foundational information about clinician perspectives that will facilitate future translational research in this area.Implications for rehabilitationCross education, or training the stronger arm to increase strength in the weaker arm, is an intervention particularly appropriate for people with stroke who have severe impairments in arm strength.This intervention should not replace the forced use paradigm, but may be a useful adjunct in rehabilitation.Therapists perceived that education of patients, families, therapists, and doctors would be critical for cross education to be implemented successfully – as it is opposite the forced use paradigm that characterizes most of stroke rehabilitation.

Restricted Blood Flow Exercise in Sedentary, Overweight African-American Females May Increase Muscle Strength and Decrease Endothelial Function and Vascular Autoregulation.

Objectives:Exercise with partially restricted blood flow is a low-load, low-intensity resistance training regimen which may have the potential to increase muscle strength in the obese, elderly and frail who are unable to do high-load training. Restricted blood flow exercise has also been shown to affect blood vessel function variably and can, therefore, contribute to blood vessel dysfunction. This pilot study tests the hypothesis that unilateral resistance training of the leg extensors with partially restricted blood flow increases muscle strength and decreases vascular autoregulation.Methods:The subjects were nine normotensive, overweight, young adult African-Americans with low cardiorespiratory fitness who underwent unilateral training of the quadriceps’ femoris muscles with partially restricted blood flow at 30% of the 1-repetition maximum (1-RM) load for 3 weeks. The 1-RM load and post-occlusion blood flow to the lower leg (calf) were measured during reactive hyperemia.Results:The 1-RM load increased in the trained legs from 77 ± 3 to 84 ± 4 kg (P < 0.05) in the absence of a significant effect on the 1-RM load in the contralateral untrained legs (P > 0.1). Post-occlusion blood flow decreased significantly in the trained legs from 19 ± 2 to 13 ± 2 mL· min-1· dL-1 (P < 0.05) and marginally in the contralateral untrained legs from 18 ± 2 to 16 ± 1 mL· min-1· dL-1 (P = 0.09). Changes in post-occlusion blood flow to the skin overlying the trained and the contralateral untrained muscles were not significant.Conclusion:These results demonstrate that restricted blood flow exercise, which results in significant gains in muscle strength, may produce decrements in endothelial dysfunction and vascular autoregulation. Future studies should determine whether pharmacopuncture plays a role in treatments for such blood vessel dysfunction.

Effects of nitrate supplementation in trained and untrained muscle are modest with initial high plasma nitrite levels.

Nitrate (NO3-) supplementation resulting in higher plasma nitrite (NO2-) is reported to lower resting mean arterial blood pressure (MAP) and oxygen uptake (VO2 ) during submaximal exercise in non-athletic populations, whereas effects in general are absent in endurance-trained individuals. To test whether physiologic effects of NO3- supplementation depend on local muscular training status or cardiovascular fitness, male endurance-trained cyclists (CYC, n=9, VO2 -max: 64±3mL/min/kg; mean±SD) and recreational active subjects serving as a control group (CON, n=8, 46±3mL/min/kg), acutely consumed nitrate-rich beetroot juice ([NO3-] ~9mmol) (NIT) or placebo (PLA) with assessment of resting MAP and energy expenditure during moderate intensity (~50% VO2 -max) and incremental leg cycling (LEG-ex) and arm-cranking exercise (ARM-ex). NIT increased (P<.001) resting plasma NO3- by ~1200% relative to PLA. Plasma NO2- increased ~25% (P<.01) with a significant change only in CYC. LEG-ex VO2 (~2.60L/min), ARM-ex VO2 (~1.14L/min), and resting MAP (~87mm Hg) remained unchanged for CYC, and similarly for CON, no changes were observed for LEG-ex VO2 (~2.03L/min), ARM-ex VO2 (~1.06L/min), or resting MAP (~85mm Hg). VO2 -max was not affected by supplementation, but incremental test peak power was higher (P<.05) in LEG-ex for CYC in NIT relative to PLA (418±47 vs 407±46W). In both CYC and CON, high initial baseline values and small increases in plasma NO2- after NIT may have lowered the effect of the intervention implying that muscular and cardiovascular training status is likely not the only factors that influence the physiologic effects of NO3- supplementation.

Slow breathing training reduces resting blood pressure and the pressure responses to exercise.

Slow breathing training reduces resting blood pressure, probably by modifying central autonomic control, but evidence for this is lacking. The pressor response to static handgrip exercise is a measure of autonomic control and the aim of this study was to determine whether slow breathing training modulates the pressor responses to exercise of untrained muscles. Twenty hypertensive patients trained for 8 weeks, 10 with unloaded slow breathing (Unloaded) and 10 breathing against an inspiratory load of 20 cm H(2)O (Loaded). Ten subjects were untrained controls. Subjects performed a 2 min handgrip pressor test (30 % MVC) pre- and post-training, and blood pressure and heart rate (HR) were measured before the contraction, at the end and following 2 min recovery. Resting systolic (sBP) and HR were reduced as a result of training, as reported previously. After training there was both a smaller pressor response to hand grip exercise and a more rapid recovery of sBP and HR compared to pre-training. There were no changes in the Controls and no differences between the Unloaded and Loaded groups. Combining the two training groups, the sBP response to handgrip exercise after training was reduced by 10 mm Hg (95 % CI: -7, -13) and HR by 5 bpm (95 % CI: -4, -6), all p<0.05. These results are consistent with slow breathing training modifying central mechanisms regulating cardiovascular function.