scholarly journals Investigating human skeletal muscle physiology with unilateral exercise models: when one limb is more powerful than two

2017 ◽  
Vol 42 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Martin J. MacInnis ◽  
Chris McGlory ◽  
Martin J. Gibala ◽  
Stuart M. Phillips

Direct sampling of human skeletal muscle using the needle biopsy technique can facilitate insight into the biochemical and histological responses resulting from changes in exercise or feeding. However, the muscle biopsy procedure is invasive, and analyses are often expensive, which places pragmatic restraints on sample sizes. The unilateral exercise model can serve to increase statistical power and reduce the time and cost of a study. With this approach, 2 limbs of a participant are randomized to 1 of 2 treatments that can be applied almost concurrently or sequentially depending on the nature of the intervention. Similar to a typical repeated measures design, comparisons are made within participants, which increases statistical power by reducing the amount of between-person variability. A washout period is often unnecessary, reducing the time needed to complete the experiment and the influence of potential confounding variables such as habitual diet, activity, and sleep. Variations of the unilateral exercise model have been employed to investigate the influence of exercise, diet, and the interaction between the 2, on a wide range of variables including mitochondrial content, capillary density, and skeletal muscle hypertrophy. Like any model, unilateral exercise has some limitations: it cannot be used to study variables that potentially transfer across limbs, and it is generally limited to exercises that can be performed in pairs of treatments. Where appropriate, however, the unilateral exercise model can yield robust, well-controlled investigations of skeletal muscle responses to a wide range of interventions and conditions including exercise, dietary manipulation, and disuse or immobilization.

2013 ◽  
Vol 304 (6) ◽  
pp. R450-R458 ◽  
Author(s):  
Jonathan D. Bartlett ◽  
Jari Louhelainen ◽  
Zafar Iqbal ◽  
Andrew J. Cochran ◽  
Martin J. Gibala ◽  
...  

The mechanisms that regulate the enhanced skeletal muscle oxidative capacity observed when training with reduced carbohydrate (CHO) availability are currently unknown. The aim of the present study was to test the hypothesis that reduced CHO availability enhances p53 signaling and expression of genes associated with regulation of mitochondrial biogenesis and substrate utilization in human skeletal muscle. In a repeated-measures design, muscle biopsies (vastus lateralis) were obtained from eight active males before and after performing an acute bout of high-intensity interval running with either high (HIGH) or low CHO availability (LOW). Resting muscle glycogen (HIGH, 467 ± 19; LOW, 103 ± 9 mmol/kg dry wt) was greater in HIGH compared with LOW ( P < 0.05). Phosphorylation (P-) of ACCSer79 (HIGH, 1.4 ± 0.4; LOW, 2.9 ± 0.9) and p53Ser15 (HIGH, 0.9 ± 0.4; LOW, 2.6 ± 0.8) was higher in LOW immediately postexercise and 3 h postexercise, respectively ( P < 0.05). Before and 3 h postexercise, mRNA content of pyruvate dehydrogenase kinase 4, mitochondrial transcription factor A, cytochrome- c oxidase IV, and PGC-1α were greater in LOW compared with HIGH ( P < 0.05), whereas carnitine palmitoyltransferase-1 showed a trend toward significance ( P = 0.09). However, only PGC-1α expression was increased by exercise ( P < 0.05), where three-fold increases occurred independently of CHO availability. We conclude that the exercise-induced increase in p53 phosphorylation is enhanced in conditions of reduced CHO availability, which may be related to upstream signaling through AMPK. Given the emergence of p53 as a molecular regulator of mitochondrial biogenesis, such nutritional modulation of contraction-induced p53 activation has implications for both athletic and clinical populations.


Methodology ◽  
2017 ◽  
Vol 13 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Pablo Livacic-Rojas ◽  
Guillermo Vallejo ◽  
Paula Fernández ◽  
Ellián Tuero-Herrero

Abstract. Low precision of the inferences of data analyzed with univariate or multivariate models of the Analysis of Variance (ANOVA) in repeated-measures design is associated to the absence of normality distribution of data, nonspherical covariance structures and free variation of the variance and covariance, the lack of knowledge of the error structure underlying the data, and the wrong choice of covariance structure from different selectors. In this study, levels of statistical power presented the Modified Brown Forsythe (MBF) and two procedures with the Mixed-Model Approaches (the Akaike’s Criterion, the Correctly Identified Model [CIM]) are compared. The data were analyzed using Monte Carlo simulation method with the statistical package SAS 9.2, a split-plot design, and considering six manipulated variables. The results show that the procedures exhibit high statistical power levels for within and interactional effects, and moderate and low levels for the between-groups effects under the different conditions analyzed. For the latter, only the Modified Brown Forsythe shows high level of power mainly for groups with 30 cases and Unstructured (UN) and Autoregressive Heterogeneity (ARH) matrices. For this reason, we recommend using this procedure since it exhibits higher levels of power for all effects and does not require a matrix type that underlies the structure of the data. Future research needs to be done in order to compare the power with corrected selectors using single-level and multilevel designs for fixed and random effects.


2003 ◽  
Vol 285 (6) ◽  
pp. H2382-H2391 ◽  
Author(s):  
B. J. McGuire ◽  
T. W. Secomb

A previously developed Krogh-type theoretical model was used to estimate capillary density in human skeletal muscle based on published measurements of oxygen consumption, arterial partial pressure of oxygen, and blood flow during maximal exercise. The model assumes that oxygen consumption in maximal exercise is limited by the ability of capillaries to deliver oxygen to tissue and is therefore strongly dependent on capillary density, defined as the number of capillaries per unit cross-sectional area of muscle. Based on an analysis of oxygen transport processes occurring at the microvascular level, the model allows estimation of the minimum number of straight, evenly spaced capillaries required to achieve a given oxygen consumption rate. Estimated capillary density values were determined from measurements of maximal oxygen consumption during knee extensor exercise and during whole body cycling, and they range from 459 to 1,468 capillaries/mm2. Measured capillary densities, obtained with either histochemical staining techniques or electron microscopy on quadriceps muscle biopsies from healthy subjects, are generally lower, ranging from 123 to 515 capillaries/mm2. This discrepancy is partly accounted for by the fact that capillary density decreases with muscle contraction and muscle biopsy samples typically are strongly contracted. The results imply that estimates of maximal oxygen transport rates based on capillary density values obtained from biopsy samples do not fully reflect the oxygen transport capacity of the capillaries in skeletal muscle.


2015 ◽  
Vol 309 (4) ◽  
pp. E388-E397 ◽  
Author(s):  
Adam J. Trewin ◽  
Leonidas S. Lundell ◽  
Ben D. Perry ◽  
Kim Vikhe Patil ◽  
Alexander V. Chibalin ◽  
...  

—Reactive oxygen species (ROS) produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise; however, the effects of exercise-induced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7–14 days apart, 55 min at 65% V̇o2peak plus 5 min at 85%V̇o2peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min−1·m2) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and post-insulin clamp (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS/protein carbonylation ratio by −13.5% ( P = 0.08) and increase the GSH/GSSG ratio twofold vs. CON ( P < 0.05). Insulin sensitivity was reduced (−5.9%, P < 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON ( P < 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.


2018 ◽  
Author(s):  
Blair Saunders ◽  
Anja Riesel ◽  
Julia Klawohn ◽  
Michael Inzlicht

Touch is central to mammalian communication, socialisation, and wellbeing. Despite this prominence, interpersonal touch is relatively understudied. In this preregistered investigation, we assessed the influence of interpersonal touch on the subjective, neural, and behavioural correlates of cognitive control. Forty-five romantic couples were recruited (N=90; dating&gt;6 months), and one partner performed an inhibitory control task while electroencephalography was recorded to assess neural performance monitoring. Interpersonal touch was provided by the second partner, and was manipulated between experimental blocks. A within-subject repeated-measures design was used to maximise statistical power, with our sample size providing 80% power for even small effect sizes (ds &gt; .25). Results indicated that participants were not only happier when receiving touch, but also showed increased neural processing of mistakes. Further exploratory cognitive modelling using indirect effects tests and drift diffusion models of decision making revealed that touch was indirectly associated with both improved inhibitory control and increased rates of evidence accumulation (drift rate) through its influence on neural monitoring. Thus, beyond regulating emotion and stress, interpersonal touch appears to enhance the neurocognitive processes underling flexible goal-directed behaviour.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mohd-Firdaus Maasar ◽  
Daniel C. Turner ◽  
Piotr P. Gorski ◽  
Robert A. Seaborne ◽  
Juliette A. Strauss ◽  
...  

The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g., high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in five male sport team members using a repeated measures design of: (1) change of direction (COD) versus; (2) straight line (ST) running exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 min and 24 h post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed × distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) exertion measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 min and 24 h post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 min post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We also confirmed increased gene expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes PPARGC1A (that encodes PGC1-α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via COD exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise.


2019 ◽  
Author(s):  
Konstantinos Papanikolaou ◽  
Dimitrios Draganidis ◽  
Athanasios Chatzinikolaou ◽  
Vassiliki C. Laschou ◽  
Kalliopi Georgakouli ◽  
...  

Abstract Background Muscle satellite cells (SCs) are crucial for muscle regeneration following muscle trauma. Acute skeletal muscle damage results in inflammation and production of reactive oxygen species (ROS) which may be implicated in SCs activation. Protection of these cells from oxidative damage is essential to ensure sufficient muscle regeneration. The aim of this study is to determine whether SCs activity under conditions of aseptic skeletal muscle trauma induced by exercise is redox-dependent. Methods/design Based on their SCs content in their vastus lateralis skeletal muscle, participants will be classified as either high or low respondents. In a randomized, double-blind, crossover, repeated measures design, participants will then receive either Placebo or N-acetylcysteine (alters redox potential in muscle) during a preliminary 7-day loading phase, and for 8 consecutive days following a single bout of intense muscle-damaging exercise. In both trials, blood samples and muscle biopsies will be collected, and muscle performance and soreness will be measured at baseline, pre-exercise, 2- and 8-days post-exercise. Biological samples will be analyzed for redox status and SCs activity. Between trials, a 4-week washout period will be implemented. Discussion This study is designed to investigate the impact of redox status on SCs mobilization and thus skeletal muscle potential for regeneration under conditions of aseptic inflammation induced by exercise. Findings of this trial will provide insight into i) molecular pathways involved in SCs recruitment and muscle healing under conditions of aseptic skeletal muscle trauma present in numerous catabolic conditions and ii) if skeletal muscle’s potential for regeneration depends on its basal SCs content.


2017 ◽  
Vol 42 (6) ◽  
pp. 656-666 ◽  
Author(s):  
Jacob T. Bonafiglia ◽  
Brittany A. Edgett ◽  
Brittany L. Baechler ◽  
Matthew W. Nelms ◽  
Craig A. Simpson ◽  
...  

The purpose of the present study was to determine if acute responses in PGC-1α, VEGFA, SDHA, and GPD1–2 mRNA expression predict their associated chronic skeletal muscle molecular (SDH–GPD activity and substrate storage) and morphological (fibre-type composition and capillary density) adaptations following training. Skeletal muscle biopsies were collected from 14 recreationally active men (age: 22.0 ± 2.4 years) before (PRE) and 3 h after (3HR) the completion of an acute bout of sprint interval training (SIT) (eight 20-s intervals at ∼170% peak oxygen uptake work rate separated by 10 s of recovery). Participants then completed 6 weeks of SIT 4 times per week with additional biopsies after 2 (MID) and 6 (POST) weeks of training. Acute increases in PGC-1α mRNA strongly predicted increases in SDH activity (a marker of oxidative capacity) from PRE and MID to POST (PRE–POST: r = 0.81, r2 = 0.65, p < 0.01; MID–POST: r = 0.79, r2 = 0.62, p < 0.01) and glycogen content from MID to POST (r = 0.60, r2 = 0.36, p < 0.05). No other significant relationships were found between acute responses in PGC-1α, VEGFA, SDHA, and GPD1–2 mRNA expression and chronic adaptations to training. These results suggest that acute upregulation of PGC-1α mRNA relates to the magnitude of subsequent training-induced increases in oxidative capacity, but not other molecular and morphological chronic skeletal muscle adaptations. Additionally, acute mRNA responses in PGC-1α correlated with VEGFA, but not SDHA, suggesting a coordinated upregulation between PGC-1α and only some of its proposed targets in human skeletal muscle.


2011 ◽  
Vol 111 (5) ◽  
pp. 1448-1458 ◽  
Author(s):  
Robyn M. Murphy ◽  
Kristian Vissing ◽  
Heidy Latchman ◽  
Cedric Lamboley ◽  
Michael J. McKenna ◽  
...  

The skeletal muscle-specific calpain-3 protease is likely involved in muscle repair, although the mechanism is not known. Physiological activation of calpain-3 occurs 24 h following eccentric exercise in humans. Functional consequences of calpain-3 activation are not known; however, calpain-3 has been suggested to be involved in nuclear signaling via NF-κB. To test this and help identify how/where calpain-3 acts, we investigated whether calpain-3 autolysis (hence, activation) following eccentric exercise results in translocation from its normal myofibrillar location to the nucleus or the cytosol. In resting human skeletal muscle, the majority (87%) of calpain-3 was present in myofibrillar fractions, with only a small proportion (<10%) in an autolyzed state. Enriched nuclear fractions contained ∼8% of the total calpain-3, which was present in a predominantly (>80%) autolyzed state. Using freshly dissected human muscle fibers to identify freely diffusible proteins, we showed that only ∼5% of the total calpain-3 pool was cytosolic. At 3 and 24 h following eccentric step exercise, there was an ∼70% increase in autolysis in whole muscle samples ( n = 11, P < 0.05, by 1-way ANOVA with repeated measures and Newman-Keuls post hoc analysis). This exercise-induced autolysis was attributed to myofibrillar-bound calpain-3, since neither the amount of calpain-3 nor the proportion autolyzed was significantly changed in enriched nuclear or cytosolic fractions following the exercise intervention. We present a model for calpain-3 localization at rest and following activation in human skeletal muscle and suggest that the functional importance of calpain-3 remains predominantly tightly associated with its localization within the myofibrillar compartment.


2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Nur Al Ali ◽  
Andres Arriaga ◽  
Margarita Rubio

Purpose The purpose of this paper is to design a culinary education program and ascertain its impact on knowledge, phobias, culinary skills and diet quality in schoolchildren. Design/methodology/approach Repeated measures design to determine changes after the implementation of the culinary education program in a pre-school and primary school located in a Madrid (Spain) neighborhood with a low socioeconomic level. A total of 58 children agreed to participate in the program and 40 parents authorized the evaluation of the effect of the program. Variables were measured with Student’s t-test or Wilcoxon-signed range test for quantitative variables. Effect size was calculated by Cohen’s d. Findings The mean scores in knowledge and beliefs improved from 5.0 to 7.8 (P < 0.001; Cohen’s d = 1), the mean value obtained in the food phobias test decreased from 24.6 to 20.7 (P = 0.01; Cohen’s d = 0.53), diet quality on Kid Med Test score increased from 7.4 to 8.2 (P = 0.06; Cohen’s d = 0.38), and the children improved their culinary skills from 21.2 to 27.9 (P < 0.001; Cohen’s d = 0.66). Research limitations/implications Self-declared data could lead to information biases. Other limitations were the lack of control group and a scarce statistical power that could explain the absence of statistical significance in the results on diet quality. To observe the effects of this change on eating habits, long-term evaluations would have to be carried out. Originality/value The brand-new culinary education program had a positive effect on children’s knowledge of nutrition and culinary skills as well as reducing food phobias. This proposal is beyond the state-of-the-art and could be implemented elsewhere with a robust effect on children, parents and educators.


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