Six weeks of high-load resistance and low-load blood flow restricted training increase Na/K-ATPase sub-units α2 and ß1 equally, but does not alter ClC-1 abundance in untrained human skeletal muscle.

Contractile function of skeletal muscle relies on the ability of muscle fibers to trigger and propagate action potentials (APs). These electrical signals are created by transmembrane ion transport through ion channels and membrane transporter systems. In this regard, the Cl- ion channel 1 (ClC-1) and the Na+/K--ATPase (NKA) are central for maintaining ion homeostasis across the sarcolemma during intense contractile activity. Therefore, this randomized controlled trial aimed to investigate the changes in ClC-1 and specific NKA subunit isoform expression in response to six weeks (18 training sessions) of high-load resistance exercise (HLRE) and low-load blood flow restricted resistance exercise (BFRRE), respectively. HLRE was conducted as 4 sets of 12 repetitions of knee extensions performed at 70% of 1 repetition maximum (RM), while BFRRE was conducted as 4 sets of knee extensions at 30% of 1RM performed to volitional fatigue. Furthermore, the potential associations between protein expression and contractile performance were investigated. We show that muscle ClC-1 abundance was not affected by either exercise modality, whereas NKA subunit isoforms [Formula: see text]2 and [Formula: see text]1 increased equally by appx. 80-90% with BFRRE (p < 0.05) and 70-80% with HLRE (p < 0.05). No differential impact between exercise modalities was observed. At baseline, ClC-1 protein expression correlated inversely with dynamic knee extensor strength (r=-0.365, p = 0.04), whereas no correlation was observed between NKA subunit content and contractile performance at baseline. However, training-induced changes in NKA [Formula: see text]2 subunit (r = 0.603, p < 0.01) and [Formula: see text]1 subunit (r = 0.453, p < 0.05) correlated with exercise-induced changes in maximal voluntary contraction. These results suggest that the initial adaptation to resistance-based exercise does not involve changes in ClC-1 abundance in untrained skeletal muscle, and that increased content of NKA subunits may facilitate increases in maximal force production.

Prolonged loss of force and power following fatiguing contractions in rat soleus muscles. Is low-frequency fatigue an issue during dynamic contractions?

Low-frequency fatigue (LFF) is defined by a relatively larger deficit in isometric force elicited by low-frequency electrical stimulation compared with high-frequency stimulation. However, the effects of LFF on power during dynamic contractions elicited at low and high frequencies have not been thoroughly characterized. In the current study, rat soleus muscles underwent fatiguing either concentric, eccentric, or isometric contractions. Before and 1 h after the fatiguing contractions, a series of brief isometric and dynamic contractions elicited at 20 and 80 Hz stimulation to establish force-velocity relationships. Maximal force (Fmax), velocity (Vmax), and power (Pmax) were assessed for each frequency. Sarcoplasmic reticulum (SR) Ca2+ release and reuptake rates were assessed pre- and postfatigue. Prolonged fatigue was observed as a loss of Fmax and Pmax in muscles fatigued by concentric or eccentric, but not by isometric contractions. When quantified as a decrease in the ratio between 20 Hz and 80 Hz contractile output, LFF was more pronounced for isometric force than for power (-21% vs. -16% for concentrically fatigued muscles, P = 0.003; 29 vs. 13% for eccentrically fatigued muscles, P < 0.001). No changes in SR Ca2+ release or reuptake rates were observed. We conclude that LFF is less pronounced when expressed in terms of power deficits than when expressed in terms of force deficits, and that LFF, therefore, likely affects performance to a lesser degree during fast concentric contractions than during static or slow contractions.

Protein signalling in response to ex vivo dynamic contractions is independent of training status in rat skeletal muscle.

NEW FINDINGS: What is the central question of this study? Are myofibre protein signalling responses to ex vivo dynamic contractions altered by accustomization to voluntary endurance training in rats? What is the main finding and its importance? In response to ex vivo dynamic muscle contractions, canonical myofibre protein signalling pertaining to metabolic transcriptional regulation, as well as translation initiation and elongation, was not influenced by prior accustomization to voluntary endurance training in rats. Accordingly, intrinsic myofibre protein signalling responses to standardized contractile activity may be independent of prior exercise training in rat skeletal muscle. ABSTRACT: Skeletal muscle training status may influence myofibre regulatory protein signalling in response to contractile activity. The current study employed a purpose-designed ex vivo dynamic contractile protocol to evaluate the effect of exercise-accustomization on canonical myofibre protein signalling for metabolic gene expression and for translation initiation and elongation. To this end, rats completed 8 weeks of in vivo voluntary running training versus no running control intervention, whereupon an ex vivo endurance-type dynamic contraction stimulus was conducted in isolated soleus muscle preparations from both intervention groups. Protein signalling response by phosphorylation was evaluated by immunoblotting at 0 and 3 h following ex vivo stimulation. Phosphorylation of AMP-activated protein kinase α-isoforms and its downstream target, acetyl-CoA carboxylase, as well as phosphorylation of eukaryotic elongation factor 2 (eEF2) was increased immediately following the dynamic contraction protocol (at 0 h). Signalling for translation initiation and elongation was evident at 3 h after dynamic contractile activity, as evidenced by increased phosphorylation of p70 S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1, as well as a decrease in phosphorylation of eEF2 back to resting control levels. However, prior exercise training did not alter phosphorylation responses of the investigated signalling proteins. Accordingly, protein signalling responses to standardized endurance-type contractions may be independent of training status in rat muscle during ex vivo conditions. The present findings add to our current understanding of molecular regulatory events responsible for skeletal muscle plasticity.

The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance.

Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification.

Utilization of biomarkers as predictors of skeletal muscle mitochondrial content after physiological intervention and in clinical settings.

The measurement of mitochondrial content is essential for bioenergetic research, as it provides a tool to evaluate whether changes in mitochondrial function are strictly due to changes in content or other mechanisms that influence function. In this perspective, we argue that commonly used biomarkers of mitochondrial content may possess limited utility for capturing changes in content with physiological intervention. Moreover, we argue that they may not provide reliable estimates of content in certain pathological situations. Finally, we discuss potential solutions to overcome issues related to the utilization of biomarkers of mitochondrial content. Shedding light on this important issue will hopefully aid conclusions about the mitochondrial structure-function relationship.

Myocellular Adaptations to Low-Load Blood Flow Restricted Resistance Training.

Low-load blood flow restricted resistance exercise (BFRRE) can stimulate whole-muscle growth and improve muscle function. However, limited knowledge exists on the effects at the myocellular level. We hypothesize that BFRRE has the ability to produce concurrent skeletal muscle myofibrillar, mitochondrial, and microvascular adaptations, thus offering an alternative strategy to counteract decay in skeletal muscle health and function in clinical populations.

Non-failure blood flow restricted exercise induces similar muscle adaptations and less discomfort than failure protocols.

Low-load blood flow restricted resistance exercise (BFRE) performed to volitional failure is suggested to constitute an effective method for producing increases in muscle size and function. However, BFRE to failure may entail high levels of perceived exertion, discomfort, and/or delayed onset of muscle soreness (DOMS). The aim of the study was to compare BFRE performed to volitional failure (F-BFRE) vs non-failure BFRE (NF-BFRE) on changes in muscle size, function and perceptual responses. Fourteen young untrained males had one leg randomized to knee extension F-BFRE while the contralateral leg performed NF-BFRE. The training consisted of 22 exercise bouts over an 8-week period. Whole-muscle cross-sectional area (CSA) of quadriceps components, muscle function, and DOMS were assessed before and after the training period. Perceived exertion and discomfort were registered during each exercise bout. Both F-BFRE and NF-BFRE produced regional increases in muscle CSA in the range of: quadriceps (2.5%-3.8%), vastus lateralis (8.1%-8.5%), and rectus femoris (7.9%-25.0%). All without differences between leg. Muscle strength (6.8%-11.5%) and strength-endurance capacity (13.9%-18.6%) also increased to a similar degree in both legs. Less perceived exertion, discomfort, and DOMS were reported with NF-BFRE compared to F-BFRE. In conclusion, non-failure BFRE enables increases in muscle size and muscle function, while involving reduced perceptions of exertion, discomfort, and DOMS. Non-failure BFRE may be a more feasible approach in clinical settings.

Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic resonance imaging (MRI) and clinical measures of disease progression in people with MS. METHODS: This study was a 24-week randomised controlled cross-over trial, including a Training ( n = 18, 24 weeks of PRT followed by self-guided physical activity) and Waitlist group ( n = 17, 24 weeks of habitual lifestyle followed by PRT). Assessments included disability measures and MRI (lesion load, global brain volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS: While the MS Functional Composite score improved, Expanded Disability Status Scale, lesion load and global brain volumes did not differ between groups. PBVC tended to differ between groups and higher absolute cortical thickness values were observed in 19 of 74 investigated cortical regions after PRT. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups for four areas: anterior cingulate gyrus, temporal pole, orbital sulcus and inferior temporal sulcus. CONCLUSION: PRT seem to induce an increase in cortical thickness, indicating that PRT have a neuroprotective or even neuroregenerative effect in relapsing-remitting MS.

Skeletal muscle stem cell characteristics and myonuclei content in patients with rheumatoid arthritis: a cross-sectional study.

To investigate satellite cells (SCs) and myonuclei characteristics in patients with rheumatoid arthritis (RA). Resting biopsies from m. vastus lateralis were obtained from thirteen RA patients and thirteen matched healthy controls (CON). Muscle biopsies were immunohistochemically stained and analyzed for fiber type specific content of SCs (Pax7+), proliferating SCs (Pax7+/MyoD+) and differentiating SCs (myogenin+). Furthermore, we quantified fiber type specific content of myonuclei and myofiber cross-sectional area (CSA). Finally, newly formed/regenerating fibers expressing neonatal MHC (nMHC+) were determined. The fiber type specific number of SCs did not differ between RA patients and CON, nor did the content of proliferating or differentiating SCs. In contrast, the content of myonuclei per fiber was higher in RA patients than CON for both type I (2.01 ± 0.41 vs. 1.42 ± 0.40 myonuclei/fiber, p < 0.01) and type II fibers (2.01 ± 0.41 vs. 1.37 ± 0.32 myonuclei/fiber, p < 0.01). No differences were observed in fiber composition, fiber type specific CSA or content of nMHC+ fibers. Our results indicate an increased propensity for myogenic differentiation of SC leading to an elevated myonuclear content in the skeletal muscle of RA patients. It is hypothesized that this could be a compensatory regulatory response related to the chronic inflammation in these patients.

Body position influences arterial occlusion pressure: implications for the standardization of pressure during blood flow restricted exercise.

PURPOSE: Arterial occlusion pressure (AOP) measured in a supine position is often used to set cuff pressures for blood flow restricted exercise (BFRE). However, supine AOP may not reflect seated or standing AOP, thus potentially influencing the degree of occlusion. The primary aim of the study was to investigate the effect of body position on AOP. A secondary aim was to investigate predictors of AOP using wide and narrow cuffs. METHODS: Twenty-four subjects underwent measurements of thigh circumference, skinfold and blood pressure, followed by assessments of thigh AOP in supine and seated positions with a wide and a narrow cuff, respectively, using Doppler ultrasound. RESULTS: In the supine position, AOP was 148 ± 19 and 348 ± 94 mmHg with the wide and narrow cuff, respectively. This increased to 177 ± 20 and 409 ± 101 mmHg in the seated position, with correlations between supine and seated AOP of R 2 = 0.81 and R 2 = 0.50 for the wide and narrow cuff, respectively. For both cuff widths, thigh circumference constituted the strongest predictor of AOP, with diastolic blood pressure explaining additional variance with the wide cuff. The predictive strength of these variables did not differ between body positions. CONCLUSION: Our results indicate that body position strongly influences lower limb AOP, especially with narrow cuffs, yielding very high AOP (≥ 500-600 mmHg) in some subjects. This should be taken into account in the standardization of cuff pressures used during BFRE to better control the physiological effects of BFRE.

Contraction mode and whey protein intake affect the synthesis rate of intramuscular connective tissue.

INTRODUCTION: In this study we investigated the impact of whey protein hydrolysate and maltodextrin (WPH) intake on intramuscular connective tissue (IMCT) protein fractional synthesis rate (FSR) after maximal shortening and lengthening contractions. METHODS: Twenty young men were randomized to receive either WPH or maltodextrin [carbohydrate (CHO)] immediately after completion of unilateral shortening and lengthening knee extensions. Ring-13 C6 -phenylalanine was infused, and muscle biopsies were obtained. IMCT protein FSR was measured at 1-5, as well as 1-3 and 3-5 hours after contractions and nutrient intake. RESULTS: During the 1-3-hour recovery, lengthening contractions resulted in a higher FSR than shortening contractions (P < 0.01), independent of supplementation type and, during the 3-5-hour recovery, WPH had a higher FSR than CHO (P < 0.05), independent of prior contraction mode. CONCLUSIONS: The later appearance of a stimulating effect of WPH on the IMCT FSR after strenuous muscle contractions lends support to its ability to promote recovery of the muscle connective tissue matrix after exercise. Muscle Nerve 55: 128-130, 2017.

Muscle damage and repeated bout effect following blood flow restricted exercise.

PURPOSE: Blood-flow restricted resistance exercise training (BFRE) is suggested to be effective in rehabilitation training, but more knowledge is required about its potential muscle damaging effects. Therefore, we investigated muscle-damaging effects of BFRE performed to failure and possible protective effects of previous bouts of BFRE or maximal eccentric exercise (ECC). METHODS: Seventeen healthy young men were allocated into two groups completing two exercise bouts separated by 14 days. One group performed BFRE in both exercise bouts (BB). The other group performed ECC in the first and BFRE in the second bout. BFRE was performed to failure. Indicators of muscle damage were evaluated before and after exercise. RESULTS: The first bout in the BB group led to decrements in maximum isometric torque, and increases in muscle soreness, muscle water retention, and serum muscle protein concentrations after exercise. These changes were comparable in magnitude and time course to what was observed after first bout ECC. An attenuated response was observed in the repeated exercise bout in both groups. CONCLUSION: We conclude that unaccustomed single-bout BFRE performed to failure induces significant muscle damage. Additionally, both ECC and BFRE can precondition against muscle damage induced by a subsequent bout of BFRE.

Comparative Effects of Aerobic Training and Erythropoietin on Oxygen Uptake in Untrained Humans.

Sieljacks, P, Thams, L, Nellemann, B, Larsen, MS, Vissing, K, and Christensen, B. Comparative effects of aerobic training and erythropoietin on oxygen uptake in untrained humans. J Strength Cond Res 30(8): 2307-2317, 2016-The present study examines responses to 10 weeks of aerobic training and/or erythropoiesis-stimulating agent (ESA) treatment on maximal oxygen uptake (V[Combining Dot Above]O2max). Thirty-six healthy, untrained men were randomly assigned to sedentary-placebo (n = 9), sedentary-ESA (SE) (n = 9), training-placebo (TP) (n = 10), or training-ESA (TE) (n = 8). The participants were treated subcutaneously once weekly with ESA (darbepoietin-α, week 1-3; 40 µg and week 4-10; 20 µg) or a placebo for 10 weeks. The training consisted of supervised cycling 3 times per week for 1 hour at an average of 65% of maximal watt, with a progressive overload during the intervention period. V[Combining Dot Above]O2max, wattmax, and hematological values were measured throughout the study. In addition, the total training workload and estimated energy consumption were recorded after each training session. ESA treatment increased hemoglobin (∼11 and ∼14%, p < 0.001) and hematocrit (∼12 and ∼13%, p < 0.001) in the SE and TE groups, respectively. The relative (but not absolute) increases in V[Combining Dot Above]O2max were more pronounced (p < 0.01) in TE (27 ± 6%), compared with SE (15 ± 4%) but not TP (19 ± 4%), indicating that training is superior to ESA in stimulating V[Combining Dot Above]O2max in untrained men. The increased oxygen uptake in the TE group did not result in higher absolute training workloads than in the TP group. In untrained men, training exhibits a greater stimulus for improvements in V[Combining Dot Above]O2max than ESA treatment, without pronounced additive effects, which is supported by similar average training workloads and energy consumption in TP and TE. Thus, in untrained men, training alone seems sufficient to induce improvement in V[Combining Dot Above]O2max.

Regulation of ubiquitin proteasome pathway molecular markers in response to endurance and resistance exercise and training.

Knowledge on the effects of divergent exercise on ostensibly protein degradation pathways may be valuable for counteracting muscle wasting and for understanding muscle remodelling. This study examined mRNA and/or protein levels of molecular markers of the ubiquitin proteasome pathway (UPP), including FBXO32 (atrogin-1), MURF-1, FBXO40, FOXO1 and FOXO3. Protein substrates of atrogin-1-including EIF3F, MYOG and MYOD1-and of MURF-1-including PKM and MHC-were also measured. Subjects completed 10 weeks of endurance training (ET) or resistance training (RT) followed by a single-bout of endurance exercise (EE) or resistance exercise (RE). Following training, atrogin-1, FBXO40, FOXO1 and FOXO3 mRNA increased independently of exercise mode, whereas MURF-1 mRNA and FOXO3 protein increased following ET only. No change in other target proteins occurred post-training. In the trained state, single-bout EE, but not RE, increased atrogin-1, MURF-1, FBXO40, FOXO1, FOXO3 mRNA and FOXO3 protein. In contrast to EE, FBXO40 mRNA and protein decreased following single-bout RE. MURF-1 and FOXO1 protein levels as well as the protein substrates of atrogin-1 and MURF-1 were unchanged following training and single-bout exercise. This study demonstrates that the intracellular signals elicited by ET and RT result in an upregulation of UPP molecular markers, with a greater increase following ET. However, in the trained state, the expression levels of UPP molecular markers are increased following single-bout EE, but are less responsive to single-bout RE. This suggests that adaptations following endurance exercise training are more reliant on protein UPP degradation processes than adaptations following resistance exercise training.

Neuromuscular adaptations to long-term progressive resistance training translates to improved functional capacity for people with multiple sclerosis and is maintained at follow-up.

BACKGROUND: Progressive resistance training (PRT) is acknowledged to effectively improve muscle strength for people with multiple sclerosis (PwMS), but diverging results exist regarding whether such improvements translates to improved functional capacity, possibly relating to insufficient duration and/or intensity in some previous studies. OBJECTIVE: The purpose of this study was to evaluate potential changes in functional capacity and neuromuscular function after 24 weeks of supervised PRT, and whether improvements are maintained after an additional 24 weeks of self-guided exercise. METHODS: This study was a randomised controlled trial, with a training group and a waitlist group undergoing supervised PRT for 24 weeks initially or after 24 weeks of habitual lifestyle, respectively. Functional capacity, isometric muscle strength of knee extensors and flexors, neural drive and thigh muscle cross-sectional area was measured at baseline, after 24 and 48 weeks. RESULTS: The training group significantly improved neuromuscular function of the knee extensors and flexors, which translated to improvements in functional capacity. Furthermore, the improved functional capacity was maintained after 24 weeks of self-guided physical activity. The waitlist group produced similar patterns of changes after PRT. CONCLUSION: Compelling evidence is provided, that PRT performed over sufficiently long periods, improves functional capacity, likely due to neuromuscular adaptations.

No differential effects of divergent isocaloric supplements on signaling for muscle protein turnover during recovery from muscle-damaging eccentric exercise.

Unaccustomed high-intensity eccentric exercise (ECC) can provoke muscle damage including several days of muscle force loss. Post-exercise dietary supplementation may provide a strategy to accelerate rate of force regain by affecting mechanisms related to muscle protein turnover. The aim of the current study was to investigate if protein signaling mechanisms involved in muscle protein turnover would be differentially affected by supplementation with either whey protein hydrolysate and carbohydrate (WPH+CHO) versus isocaloric carbohydrate (CHO) after muscle-damaging ECC. Twenty-four young healthy participants received either WPH+CHO (n = 12) or CHO supplements (n = 12) during post-exercise recovery from 150 maximal unilateral eccentric contractions. Prior to, at 3 h and at 24, 48, 96 and/or 168 h post-exercise, muscle strength, muscle soreness, and Akt-mTOR and FOXO signaling proteins, were measured in an ECC exercising leg and in the contralateral non-exercise control leg (CON). After ECC, muscle force decreased by 23-27 % at 24 h post-exercise, which was followed by gradual, although not full recovery at 168 h post-exercise, with no differences between supplement groups. Phosphorylation of mTOR, p70S6K and rpS6 increased and phosphorylation of FOXO1 and FOXO3 decreased in the ECC leg, with no differences between supplement groups. Phosphorylation changes were also observed for rpS6, FOXO1 and FOXO3a in the CON leg, suggesting occurrence of remote tissue effects. In conclusion, divergent dietary supplementation types did not produce differences in signaling for muscle turnover during recovery from muscle-damaging exercise.

Erythropoietin administration alone or in combination with endurance training affects neither skeletal muscle morphology nor angiogenesis in healthy young men.

The aim was to investigate the ability of an erythropoiesis-stimulating agent (ESA), alone or in combination with endurance training, to induce changes in human skeletal muscle fibre and vascular morphology. In a comparative study, 36 healthy untrained men were randomly dispersed into the following four groups: sedentary-placebo (SP, n = 9); sedentary-ESA (SE, n = 9); training-placebo (TP, n = 10); or training-ESA (TE, n = 8). The ESA or placebo was injected once weekly. Training consisted of progressive bicycling three times per week for 10 weeks. Before and after the intervention period, muscle biopsies and magnetic resonance images were collected from the thigh muscles, blood was collected, body composition measured and endurance exercise performance evaluated. The ESA treatment (SE and TE) led to elevated haematocrit, and both ESA treatment and training (SE, TP and TE) increased maximal O2 uptake. With regard to skeletal muscle morphology, TP alone exhibited increases in whole-muscle cross-sectional area and fibre diameter of all fibre types. Also exclusively for TP was an increase in type IIa fibres and a corresponding decrease in type IIx fibres. Furthermore, an overall training effect (TP and TE) was statistically demonstrated in whole-muscle cross-sectional area, muscle fibre diameter and type IIa and type IIx fibre distribution. With regard to muscle vascular morphology, TP and TE both promoted a rise in capillary to muscle fibre ratio, with no differences between the two groups. There were no effects of ESA treatment on any of the muscle morphological parameters. Despite the haematopoietic effects of ESA, we provide novel evidence that endurance training rather than ESA treatment induces adaptational changes in angiogenesis and muscle morphology.

Whey protein supplementation accelerates satellite cell proliferation during recovery from eccentric exercise.

Human skeletal muscle satellite cells (SCs) are essential for muscle regeneration and remodeling processes in healthy and clinical conditions involving muscle breakdown. However, the potential influence of protein supplementation on post-exercise SC regulation in human skeletal muscle has not been well investigated. In a comparative human study, we investigated the effect of hydrolyzed whey protein supplementation following eccentric exercise on fiber type-specific SC accumulation. Twenty-four young healthy subjects received either hydrolyzed whey protein + carbohydrate (whey, n = 12) or iso-caloric carbohydrate (placebo, n = 12) during post-exercise recovery from 150 maximal unilateral eccentric contractions. Prior to and 24, 48 and 168 h post-exercise, muscle biopsies were obtained from the exercise leg and analyzed for fiber type-specific SC content. Maximal voluntary contraction (MVC) and serum creatine kinase (CK) were evaluated as indices of recovery from muscle damage. In type II fiber-associated SCs, the whey group increased SCs/fiber from 0.05 [0.02; 0.07] to 0.09 [0.06; 0.12] (p < 0.05) and 0.11 [0.06; 0.16] (p < 0.001) at 24 and 48 h, respectively, and exhibited a difference from the placebo group (p < 0.05) at 48 h. The whey group increased SCs/myonuclei from 4 % [2; 5] to 10 % [4; 16] (p < 0.05) at 48 h, whereas the placebo group increased from 5 % [2; 7] to 9 % [3; 16] (p < 0.01) at 168 h. MVC decreased (p < 0.001) and muscle soreness and CK increased (p < 0.001), irrespective of supplementation. In conclusion, whey protein supplementation may accelerate SC proliferation as part of the regeneration or remodeling process after high-intensity eccentric exercise.

Effects of divergent resistance exercise contraction mode and dietary supplementation type on anabolic signalling, muscle protein synthesis and muscle hypertrophy.

Greater force produced with eccentric (ECC) compared to concentric (CONC) contractions, may comprise a stronger driver of muscle growth, which may be further augmented by protein supplementation. We investigated the effect of differentiated contraction mode with either whey protein hydrolysate and carbohydrate (WPH + CHO) or isocaloric carbohydrate (CHO) supplementation on regulation of anabolic signalling, muscle protein synthesis (MPS) and muscle hypertrophy. Twenty-four human participants performed unilateral isolated maximal ECC versus CONC contractions during exercise habituation, single-bout exercise and 12 weeks of training combined with WPH + CHO or CHO supplements. In the exercise-habituated state, p-mTOR, p-p70S6K, p-rpS6 increased by approximately 42, 206 and 213 %, respectively, at 1 h post-exercise, with resistance exercise per se; whereas, the phosphorylation was exclusively maintained with ECC at 3 and 5 h post-exercise. This acute anabolic signalling response did not differ between the isocaloric supplement types, neither did protein fractional synthesis rate differ between interventions. Twelve weeks of ECC as well as CONC resistance training augmented hypertrophy with WPH + CHO group compared to the CHO group (7.3 ± 1.0 versus 3.4 ± 0.8 %), independently of exercise contraction type. Training did not produce major changes in basal levels of Akt-mTOR pathway components. In conclusion, maximal ECC contraction mode may constitute a superior driver of acute anabolic signalling that may not be mirrored in the muscle protein synthesis rate. Furthermore, with prolonged high-volume resistance training, contraction mode seems less influential on the magnitude of muscle hypertrophy, whereas protein and carbohydrate supplementation augments muscle hypertrophy as compared to isocaloric carbohydrate supplementation .

Effect of resistance exercise contraction mode and protein supplementation on members of the STARS signalling pathway.

The striated muscle activator of Rho signalling (STARS) pathway is suggested to provide a link between external stress responses and transcriptional regulation in muscle. However, the sensitivity of STARS signalling to different mechanical stresses has not been investigated. In a comparative study, we examined the regulation of the STARS signalling pathway in response to unilateral resistance exercise performed as either eccentric (ECC) or concentric (CONC) contractions as well as prolonged training; with and without whey protein supplementation. Skeletal muscle STARS, myocardian-related transcription factor-A (MRTF-A) and serum response factor (SRF) mRNA and protein, as well as muscle cross-sectional area and maximal voluntary contraction, were measured. A single-bout of exercise produced increases in STARS and SRF mRNA and decreases in MRTF-A mRNA with both ECC and CONC exercise, but with an enhanced response occurring following ECC exercise. A 31% increase in STARS protein was observed exclusively after CONC exercise (P < 0.001), while pSRF protein levels increased similarly by 48% with both CONC and ECC exercise (P < 0.001). Prolonged ECC and CONC training equally stimulated muscle hypertrophy and produced increases in MRTF-A protein of 125% and 99%, respectively (P < 0.001). No changes occurred for total SRF protein. There was no effect of whey protein supplementation. These results show that resistance exercise provides an acute stimulation of the STARS pathway that is contraction mode dependent. The responses to acute exercise were more pronounced than responses to accumulated training, suggesting that STARS signalling is primarily involved in the initial phase of exercise-induced muscle adaptations.