Transcriptomic adaptation during skeletal muscle habituation to eccentric or concentric exercise training.
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ABSTRACT:
SUBMITTER: Willis CRG
PROVIDER: S-EPMC8671437 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naïve individuals, and determine if the magnitude of any response was associated with exercise induced muscle damage. Sixteen RE naïve males were recruited, 8 underwent 2 sessions of 5x30 maximum, isokinetic knee extensions (180°.s-1) separated by 48 hrs. Muscle biopsies of the vastus lateralis were taken at baseline and 24 hrs after each exercise bout. Eight individuals acted as non-exercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray, and binding of HSP27 and αB-crystallin to insoluble proteins by immunohistochemistry as a measure of muscle damage. In control subjects, no probesets were significantly altered (FDR<0.05) and HSP27 and αB-crystallin binding remained unchanged throughout the study. In exercised subjects, significant inter-subject variability following the initial bout of RE was observed in the muscle transcriptome, with greatest changes occurring when HSP27 and αB-crystallin binding was elevated. Following the second bout of RE, the transcriptome response was more consistent among subjects revealing a cohort of probesets associated with immune activation, the suppression of oxidative metabolism and protein ubiquitination as differentially regulated. The results reveal that the initial transcriptional response to RE is highly variable in RE naïve volunteers, is associated with muscle damage, and unlikely to reflect longer-term adaptations to RE training. These results highlight the importance of considering multiple time-points when determining the transcriptional response to RE and associated physiological adaptation.
2013-11-15 | GSE45426 | GEO
Project description:We used cDNA microarrays to screen for differentially expressed genes during recovery from exercise-induced muscle damage in humans. Male subjects (n = 4) performed 300 maximal eccentric contractions, and skeletal muscle biopsy samples were analyzed at 3 h and 48 h after exercise. In total, 113 genes increased 3 h postexercise, and 34 decreased. At 48 h postexercise, 59 genes increased and 29 decreased. On the basis of these data, we chose 19 gene changes and conducted secondary analyses using real-time RT-PCR from muscle biopsy samples taken from 11 additional subjects who performed an identical bout of exercise. Real-time RT-PCR analyses confirmed that exercise-induced muscle damage led to a rapid (3 h) increase in sterol response element binding protein 2 (SREBP-2), followed by a delayed (48 h) increase in the SREBP-2 gene targets Acyl CoA:cholesterol acyltransferase (ACAT)-2 and insulin-induced gene 1 (insig-1). The expression of the IL-1 receptor, a known regulator of SREBP-2, was also elevated after exercise. Taken together, these expression changes suggest a transcriptional program for increasing cholesterol and lipid synthesis and/or modification. Additionally, damaging exercise induced the expression of protein kinase H11, capping protein Z alpha (capZalpha), and modulatory calcineurin-interacting protein 1 (MCIP1), as well as cardiac ankryin repeat protein 1 (CARP1), DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management. In summary, using DNA microarrays and RT-PCR, we have identified novel genes that respond to skeletal muscle damage, which, given the known biological functions, are likely involved in recovery from and/or adaptation to damaging exercise.
| S-EPMC2707850 | biostudies-literature
Project description:We sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naïve individuals, and determine if the magnitude of any response was associated with exercise induced muscle damage. Sixteen RE naïve males were recruited, 8 underwent 2 sessions of 5x30 maximum, isokinetic knee extensions (180°.s-1) separated by 48 hrs. Muscle biopsies of the vastus lateralis were taken at baseline and 24 hrs after each exercise bout. Eight individuals acted as non-exercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray, and binding of HSP27 and αB-crystallin to insoluble proteins by immunohistochemistry as a measure of muscle damage. In control subjects, no probesets were significantly altered (FDR<0.05) and HSP27 and αB-crystallin binding remained unchanged throughout the study. In exercised subjects, significant inter-subject variability following the initial bout of RE was observed in the muscle transcriptome, with greatest changes occurring when HSP27 and αB-crystallin binding was elevated. Following the second bout of RE, the transcriptome response was more consistent among subjects revealing a cohort of probesets associated with immune activation, the suppression of oxidative metabolism and protein ubiquitination as differentially regulated. The results reveal that the initial transcriptional response to RE is highly variable in RE naïve volunteers, is associated with muscle damage, and unlikely to reflect longer-term adaptations to RE training. These results highlight the importance of considering multiple time-points when determining the transcriptional response to RE and associated physiological adaptation. 16 healthy male subjects were recruited and attended the laboratory fasted on 4 consecutive days. Biopsies from the vastus lateralis muscle were obtained on Days 0, 1 and 3, with total RNA extracted for gene expression analysis by microarray. During this period, 8 subjects performed isokinetic leg extension exercise using an isokinetic dynamometer (180 degrees per second; maximum intensity) on two occassions (days 0 and 2). Data for 7 exercise subjects presented in this study. 8 further subjects acted as non-exercised controls and did not participate in any exercise during the study period. A number of technical replicates were included and are identified in the sample list. Insufficient muscle biopsy sample or inadequate RNA quality accounted for 8 missing data points (TechRep1 N=40 as opposed to 48).
2013-11-15 | E-GEOD-45426 | biostudies-arrayexpress
Project description:OBJECTIVES:Adequate muscle perfusion supports the transport of nutrients, oxygen and hormones into muscle fibers. Aging is associated with a substantial decrease in skeletal muscle capillarization, fiber size and oxidative capacity, which may be improved with regular physical activity. The aim of this study was to investigate the relationship between muscle capillarization and indices of muscle hypertrophy (i.e. lean mass; fiber cross sectional area (CSA)) in older adults before and after 12?weeks of progressive resistance exercise training (RET). DESIGN:Interventional study SETTING AND PARTICIPANTS: 19 subjects (10 male and 9 female; 71.1?±?4.3?years; 27.6?±?3.2 BMI) were enrolled in the study and performed a whole body RET program for 12?weeks. Subjects where then retrospectively divided into a LOW or HIGH group, based on their pre-RET capillary-to-fiber perimeter exchange index (CFPE). Physical activity level, indices of capillarization (capillaries-to-fiber ratio, C:Fi; CFPE index and capillary-to-fiber interface, LC-PF index), muscle hypertrophy, muscle protein turnover and mitochondrial function were assessed before and after RET. RESULTS:Basal capillarization (C:Fi; CFPE and LP-CF index) correlates with daily physical activity level (C:Fi, r?=?0.57, p?=?0.019; CFPE index, r?=?0.55, p?=?0.024; LC-PF index, r?=?0.56, p?=?0.022) and CFPE and LC-PF indices were also positively associated with oxidative capacity (respectively r?=?0.45, p?=?0.06; r?=?0.67, p?=?0.004). Following RET, subjects in the HIGH group underwent hypertrophy with significant improvements in muscle protein synthesis and muscle fiber CSA (p?<?0.05). However, RET did not promote muscle hypertrophy in the LOW group, but RET significantly increased muscle capillary density (p?<?0.05). CONCLUSION/IMPLICATIONS:Muscle fiber capillarization before starting an exercise training program may be predictive of the muscle hypertrophic response to RET in older adults. Increases in muscle fiber size following RET appear to be blunted when muscle capillarization is low, suggesting that an adequate initial capillarization is critical to achieve a meaningful degree of muscle adaptation to RET.
| S-EPMC6904952 | biostudies-literature
Project description:Hyperthermia is suspected of accentuating skeletal muscle injury from novel exercise, but this has not been well studied. This study examined if high muscle temperatures alters skeletal muscle injury induced by eccentric exercise (ECC). Eight volunteers (age, 22.5 ± 4.1 year; height, 169.5 ± 10.8 cm; body mass, 76.2 ± 12.6 kg), serving as their own control, and who were not heat acclimatized, completed two elbow flexor ECC trials; in one trial the biceps were heated >40°C (HEAT) and in the other trial there was no heating (NON). HEAT was applied with shortwave diathermy (100 W) for 15 min immediately before the first ECC bout and for 2 min in between each bout. Individuals were followed for 10 days after each ECC session, with a 6-week washout period between arms. The maximal voluntary isometric contraction decreased by 41 ± 17% and 46 ± 20% in the NON and HEAT trials, respectively. Bicep circumference increased by 0.07 ± 0.08 mm (4%, P = 0.04) and relaxed range of motion decreased by 11.5 ± 8.2° (30%, P < 0.001) in both trials. Serum creatine kinase peaked 72-h following ECC (NON: 6289 ± 10407; HEAT: 5486 ± 6229 IU L(-1), 38-fold increase, P < 0.01) as did serum myoglobin (NON: 362 ± 483; HEAT: 355 ± 373 μg L(-1), 13-fold increase, P < 0.03). Plasma HSP 70 was higher (P < 0.02) in HEAT after 120-h of recovery. There were no differences between treatments for plasma HSP27 and interleukins 1β, 6, and 10. The results indicate that >40°C muscle temperature does not alter skeletal muscle injury or functional impairments induced by novel ECC.
| S-EPMC4873630 | biostudies-other
Project description:Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hematopoetic (CD45?) cells were evaluated in wild type (WT) and ?7 integrin transgenic (?7Tg) mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1?CD45? stem cells were increased 2-fold in WT muscle post-exercise. The ?7 integrin regulated the presence of Sca-1? cells, with expansion occurring in ?7Tg muscle and minimal cells present in muscle lacking the ?7 integrin. Sca-1?CD45? cells isolated from ?7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs), predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7? cells and facilitated formation of eMHC?DiI? fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an ?7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the ?7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy.
| S-EPMC3256189 | biostudies-literature
Project description:Combining resistance and endurance exercises in a training regime (concurrent training) can impair improvements in muscle hypertrophy, strength, and power compared to resistance training alone. Here we aimed to characterize skeletal muscle transcriptomic changes following chronic concurrent training to determine whether contraction-induced gene expression may reveal molecular underpinnings explaining impaired adaptations. Eighteen young, healthy male participants underwent 12 weeks of resistance, endurance, or concurrent training. Maximal strength, aerobic capacity, and anaerobic power were assessed. Transcriptomics were performed on skeletal muscle biopsies obtained pre and post-intervention. Improvements to maximal anaerobic power are impaired with concurrent and endurance training. Gene expression related to plasma membrane structures was enriched while gene expression related to regulation of mRNA processing and protein degradation was suppressed with concurrent training. Considerable overlap of gene expression related to extracellular matrix remodeling was observed between concurrent and endurance training. Our results provide the first comprehensive comparison of unique and overlapping gene sets enriched following chronic resistance, endurance, and concurrent training, and reveals pathways that may have implications in relation to impaired adaptations when undertaking concurrent training.
2023-04-01 | GSE137832 | GEO
Project description:IntroductionThis study aimed to compare the efficacy of eccentrically focused resistance exercise (ECC RT) to concentrically focused resistance exercise (CNC RT) on knee osteoarthritis (OA) symptoms and strength.MethodsNinety participants consented. Participants were randomized to CNC RT, ECC RT, or a wait-list, no-exercise control group. Four months of supervised exercise training was completed using traditional weight machines (CNC RT) or modified-matched machines that overloaded the eccentric action (ECC RT). Main outcomes included one-repetition maximal strength (knee extension, leg flexion, and leg press), weekly rate of strength gain, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) total score and subscores.ResultsFifty-four participants (60-85 yr, 61% women) completed the study. Both CNC RT and ECC RT groups showed 16%-28% improvement relative to the wait-list, no-exercise control group (P = 0.003-0.005) for all leg strength measures. The rate of weekly strength gain was greater for CNC RT than for ECC RT for leg press and knee flexion (by 2.9%-4.8%; both, P < 0.05) but not knee extension (0.7%; P = 0.38). There were no significant differences in WOMAC total and subscores across groups over time. Leg press strength change was the greatest contributor to change in WOMAC total scores (R = 0.223). The change in knee flexion strength from baseline to month 4 was a significant predictor of the change in WOMAC pain subscore (F ratio = 4.84, df = 45, P = 0.032). Both modes of strength training were well tolerated.ConclusionsBoth resistance training types effectively increased leg strength. Knee flexion and knee extension muscle strength can modify function and pain symptoms irrespective of muscle contraction type. Which mode to pick could be determined by preference, goals, tolerance to the contraction type, and equipment availability.
| S-EPMC6746593 | biostudies-literature
Project description:We examined global mRNA expression using cDNA microarrays in skeletal muscle of humans before, and 3h and 48h after 300 maximal eccentric contractions. Keywords: Time course
2006-04-15 | GSE4249 | GEO
Project description:Pathological and physiological stimuli, including acute exercise, activate autophagy; however, it is unknown whether exercise training alters basal levels of autophagy and whether autophagy is required for skeletal muscle adaptation to training. We observed greater autophagy flux (i.e., a combination of increased LC3-II/LC3-I ratio and LC3-II levels and reduced p62 protein content indicating a higher rate of initiation and resolution of autophagic events), autophagy protein expression (i.e., Atg6/Beclin1, Atg7, and Atg8/LC3) and mitophagy protein Bnip3 expression in tonic, oxidative muscle compared to muscles of either mixed fiber types or of predominant glycolytic fibers in mice. Long-term voluntary running (4 wk) resulted in increased basal autophagy flux and expression of autophagy proteins and Bnip3 in parallel to mitochondrial biogenesis in plantaris muscle with mixed fiber types. Conversely, exercise training promoted autophagy protein expression with no significant increases of autophagy flux and mitochondrial biogenesis in the oxidative soleus muscle. We also observed increased basal autophagy flux and Bnip3 content without increases in autophagy protein expression in the plantaris muscle of sedentary muscle-specific Pgc-1? transgenic mice, a genetic model of augmented mitochondrial biogenesis. These findings reveal that endurance exercise training-induced increases in basal autophagy, including mitophagy, only take place if an enhanced oxidative phenotype is achieved. However, autophagy protein expression is mainly dictated by contractile activity independently of enhancements in oxidative phenotype. Exercise-trained mice heterozygous for the critical autophagy protein Atg6 showed attenuated increases of basal autophagy flux, mitochondrial content, and angiogenesis in skeletal muscle, along with impaired improvement of endurance capacity. These results demonstrate that increased basal autophagy is required for endurance exercise training-induced skeletal muscle adaptation and improvement of physical performance.
| S-EPMC4046188 | biostudies-literature