scholarly journals Impaired exercise training-induced muscle fiber hypertrophy and Akt/mTOR pathway activation in hypoxemic patients with COPD

2015 ◽  
Vol 118 (8) ◽  
pp. 1040-1049 ◽  
Author(s):  
Frédéric Costes ◽  
Harry Gosker ◽  
Léonard Feasson ◽  
Marine Desgeorges ◽  
Marco Kelders ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
C2c12 Myotubes ◽  
Chronic Obstructive ◽  
Vastus Lateralis Muscle ◽  
Cross Sectional ◽  
Gsk 3Β

Exercise training (ExTr) is largely used to improve functional capacity in patients with chronic obstructive pulmonary disease (COPD). However, ExTr only partially restores muscle function in patients with COPD, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by ExTr could be compromised in hypoxemic patients with COPD. Vastus lateralis muscle biopsies were obtained from patients with COPD who were either normoxemic ( n = 15, resting arterial Po2 = 68.5 ± 1.5 mmHg) or hypoxemic ( n = 8, resting arterial Po2 = 57.0 ± 1.0 mmHg) before and after a 2-mo ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic patients with COPD. However, ExTr increased citrate synthase and lactate dehydrogenase enzyme activities only in skeletal muscle of normoxemic patients. Similarly, muscle fiber cross-sectional area and capillary-to-fiber ratio were increased only in patients who were normoxemic. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. Phosphorylation of Akt (Ser473), GSK-3β (Ser9), and p70S6k (Thr389) was nonsignificantly increased in normoxemic patients in response to ExTr, but it was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented insulin-like growth factor-1-induced phosphorylation of Akt, GSK-3β, and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of patients with COPD in an ExTr program.

Muscle blood flow during exercise in sedentary and trained hypothyroid rats

1995 ◽  
Vol 269 (6) ◽  
pp. H1949-H1954 ◽  
Author(s):  
R. M. McAllister ◽  
M. D. Delp ◽  
K. A. Thayer ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Vastus Lateralis Muscle ◽  
Blood Flows ◽  
Vastus Intermedius

Hypothyroidism is characterized by exercise intolerance. We hypothesized that active muscle blood flow during in vivo exercise is inadequate in the hypothyroid state. Additionally, we hypothesized that endurance exercise training would restore normal blood flow during acute exercise. To test these hypotheses, rats were made hypothyroid (Hypo) over 3-4 mo with propylthiouracil. A subset of Hypo rats was trained (THypo) on a treadmill at 30 m/min (15% grade) for 60 min/day 5 days/wk over 10-15 wk. Hypothyroidism was evidenced by approximately 80% reductions in plasma triiodothyronine levels in Hypo and THypo and by 40-50% reductions in citrate synthase activities in high oxidative muscles in Hypo compared with euthyroid (Eut) rats. Training efficacy was indicated by increased (25-100%) citrate synthase activities in muscles of THypo vs. Hypo. Regional blood flows were determined by the radiolabeled microsphere method before exercise and at 1-2 min of treadmill running at 15 m/min (0% grade). Preexercise muscle blood flows were generally similar among groups. During exercise, however, flows were lower in Hypo than in Eut for high oxidative muscles such as the red section of vastus lateralis [277 +/- 24 and 153 +/- 13 (SE) ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01] and vastus intermedius (317 +/- 32 and 187 +/- 20 ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01) muscles. Training (THypo) did not normalize these flows (168 +/- 24 and 181 +/- 24 ml.min-1.100 g-1 for red section of vastus lateralis and vastus intermedius muscles, respectively). Blood flows to low oxidative muscle, such as the white section of vastus lateralis muscle, were similar among groups (21 +/- 5, 25 +/- 4, and 34 +/- 7 ml.min-1.100 g-1 for Eut, Hypo, and THypo, respectively; P = NS). These findings indicate that hypothyroidism is associated with reduced blood flow to skeletal muscle during exercise, suggesting that impaired delivery of nutrients to and/or removal of metabolites from skeletal muscle contributes to the poor exercise tolerance characteristic of hypothyroidism.

scholarly journals Cardiovascular and skeletal muscle health with lifelong exercise

2018 ◽  
Vol 125 (5) ◽  
pp. 1636-1645 ◽  
Author(s):  
Kevin J. Gries ◽  
Ulrika Raue ◽  
Ryan K. Perkins ◽  
Kaleen M. Lavin ◽  
Brittany S. Overstreet ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Aerobic Exercise ◽  
Muscle Biopsy ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Metabolic Phenotype ◽  
Vastus Lateralis Muscle ◽  
Metabolic Fitness ◽  
Lifelong Exercise

The purpose of this study was to examine the effects of aerobic lifelong exercise (LLE) on maximum oxygen consumption (V̇o2max) and skeletal muscle metabolic fitness in trained women ( n = 7, 72 ± 2 yr) and men ( n = 21, 74 ± 1 yr) and compare them to old, healthy nonexercisers (OH; women: n = 10, 75 ± 1 yr; men: n = 10, 75 ± 1 yr) and young exercisers (YE; women: n = 10, 25 ± 1 yr; men: n = 10, 25 ± 1 yr). LLE men were further subdivided based on intensity of lifelong exercise and competitive status into performance (LLE-P, n = 14) and fitness (LLE-F, n = 7). On average, LLE exercised 5 day/wk for 7 h/wk over the past 52 ± 1 yr. Each subject performed a maximal cycle test to assess V̇o2maxand had a vastus lateralis muscle biopsy to examine capillarization and metabolic enzymes [citrate synthase, β-hydroxyacyl-CoA dehydrogenase (β-HAD), and glycogen phosphorylase]. V̇o2maxhad a hierarchical pattern (YE > LLE > OH, P < 0.05) for women (44 ± 2 > 26 ± 2 > 18 ± 1 ml·kg−1·min−1) and men (53 ± 3 > 34 ± 1 > 22 ± 1 ml·kg−1·min−1) and was greater ( P < 0.05) in LLE-P (38 ± 1 ml·kg−1·min−1) than LLE-F (27 ± 2 ml·kg−1·min−1). LLE men regardless of intensity and women had similar capillarization and aerobic enzyme activity (citrate synthase and β-HAD) as YE, which were 20%–90% greater ( P < 0.05) than OH. In summary, these data show a substantial V̇o2maxbenefit with LLE that tracked similarly between the sexes, with further enhancement in performance-trained men. For skeletal muscle, 50+ years of aerobic exercise fully preserved capillarization and aerobic enzymes, regardless of intensity. These data suggest that skeletal muscle metabolic fitness may be easier to maintain with lifelong aerobic exercise than more central aspects of the cardiovascular system.NEW & NOTEWORTHY Lifelong exercise (LLE) is a relatively new and evolving area of study with information especially limited in women and individuals with varying exercise intensity habits. These data show a substantial maximal oxygen consumption benefit with LLE that tracked similarly between the sexes. Our findings contribute to the very limited skeletal muscle biopsy data from LLE women (>70 yr), and similar to men, revealed a preserved metabolic phenotype comparable to young exercisers.

Effect of short-term, high-intensity exercise training on human skeletal muscle citrate synthase maximal activity: single versus multiple bouts per session

2019 ◽  
Vol 44 (12) ◽  
pp. 1391-1394
Author(s):  
Martin J. MacInnis ◽  
Lauren E. Skelly ◽  
F. Elizabeth Godkin ◽  
Brian J. Martin ◽  
Thomas R. Tripp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Maximal Activity ◽  
High Intensity Exercise ◽  
Short Term ◽  
Significant Difference

The legs of 9 men (age 21 ± 2 years, 45 ± 4 mL/(kg·min)) were randomly assigned to complete 6 sessions of high-intensity exercise training, involving either one or four 5-min bouts of counterweighted, single-leg cycling. Needle biopsies from vastus lateralis revealed that citrate synthase maximal activity increased after training in the 4-bout group (p = 0.035) but not the 1-bout group (p = 0.10), with a significant difference between groups post-training (13%, p = 0.021). Novelty Short-term training using brief intense exercise requires multiple bouts per session to increase mitochondrial content in human skeletal muscle.

Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity

1998 ◽  
Vol 85 (1) ◽  
pp. 210-214 ◽  
Author(s):  
John P. Mattson ◽  
David C. Poole
Keyword(s):  
Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Intratracheal Instillation ◽  
Oxidative Capacity ◽  
Activity Level ◽  
Oxidative Enzyme ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Reduced Physical Activity

Skeletal muscle oxidative enzyme capacity is impaired in patients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as a consequence of the reduced physical activity level in these patients. To explore this issue, citrate synthase (CS) activity was measured in selected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con, n = 7) or elastase [emphysema (Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference between groups was found. Excised lung volume increased with emphysema (Con, 1.5 ± 0.3 g; Emp, 3.0 ± 0.3 g, P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 ± 2.0; Emp, 39.2 ± 0.8 μmol ⋅ min−1 ⋅ g wet wt−1, P < 0.05) and vastus lateralis (Con, 48.5 ± 1.5; Emp, 44.9 ± 0.8 μmol ⋅ min−1 ⋅ g wet wt−1, P < 0.05) but not in the plantaris (Con, 47.4 ± 3.9; Emp, 48.0 ± 2.1 μmol ⋅ min−1 ⋅ g wet wt−1, P < 0.05) muscle. In contrast, CS activity increased in the costal (Con, 61.1 ± 1.8; Emp, 65.1 ± 1.5 μmol ⋅ min−1 ⋅ g wet wt−1, P < 0.05) and crural (Con, 58.5 ± 2.0; Emp, 65.7 ± 2.2 μmol ⋅ min−1 ⋅ g wet wt−1, P < 0.05) regions of the diaphragm. These data indicate that emphysema per se can induce decrements in the oxidative capacity of certain nonventilatory skeletal muscles that may contribute to exercise limitations in the emphysematous patient.

Exercise adaptation attenuates VEGF gene expression in human skeletal muscle

2000 ◽  
Vol 279 (2) ◽  
pp. H772-H778 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
E. Saucedo ◽  
R. Henry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Exercise Adaptation

Angiogenesis is a component of the multifactoral adaptation to exercise training, and vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation. However, there is limited evidence supporting the role of VEGF in the exercise training response. Thus we studied mRNA levels of VEGF, using quantitative Northern analysis, in untrained and trained human skeletal muscle at rest and after a single bout of exercise. Single leg knee-extension provided the acute exercise stimulus and the training modality. Four biopsies were collected from the vastus lateralis muscle at rest in the untrained and trained conditions before and after exercise. Training resulted in a 35% increase in muscle oxygen consumption and an 18% increase in number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were similar before (0.38 ± 0.04) and after (1.2 ± 0.4) training. When muscle was untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 ± 6.7). The VEGF/18S mRNA response to acute exercise in the trained state was markedly attenuated (5.4 ± 1.3). These data support the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis and appears to be subject to a negative feedback mechanism as exercise adaptations occur.

Master Athletes

2001 ◽  
Vol 11 (s1) ◽  
pp. S196-S207 ◽  
Author(s):  
Scott Trappe
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Fiber ◽  
Physiological Data ◽  
Sporting Events ◽  
Master Athletes ◽  
Cross Sectional ◽  
Recreational Athletes ◽  
Wide Range ◽  
Senior Athletes

Over the past 3 decades, there has been a continued increase in the number of “older” participants in sporting events such as running, swimming, cycling, rowing, and weightlifting. Some master athletes come from a background with years of training and competition experience, while others have only begun to compete as they approach middle-aged and older. The majority of what we currently know about master athletes and aging has been gained from both cross-sectional and longitudinal testing and re-testing master athletes and recreational athletes. The focus of this paper is on the physiological profile of athletes and individuals performing regular exercise training. Physiological data from elite and non-elite, recreational, sedentary, and senior athletes clearly indicate that human skeletal muscle has a high degree of plasticity that is maintained late into life. Muscle fiber protein expression and single muscle fiber contractile properties are greatly influenced by exercise training. It appears that skeletal muscle can quickly adapt to accommodate a wide range of functionality to meet the demands (or lack of demands) placed upon it.

scholarly journals New records in aerobic power among octogenarian lifelong endurance athletes

2013 ◽  
Vol 114 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Scott Trappe ◽  
Erik Hayes ◽  
Andrew Galpin ◽  
Leonard Kaminsky ◽  
Bozena Jemiolo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aerobic Capacity ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Endurance Athletes ◽  
Whole Body ◽  
Oxidative Enzymes ◽  
Vastus Lateralis Muscle ◽  
Peroxisome Proliferator ◽  
Mrna Targets

We examined whole body aerobic capacity and myocellular markers of oxidative metabolism in lifelong endurance athletes [ n = 9, 81 ± 1 yr, 68 ± 3 kg, body mass index (BMI) = 23 ± 1 kg/m2] and age-matched, healthy, untrained men ( n = 6; 82 ± 1 y, 77 ± 5 kg, BMI = 26 ± 1 kg/m2). The endurance athletes were cross-country skiers, including a former Olympic champion and several national/regional champions, with a history of aerobic exercise and participation in endurance events throughout their lives. Each subject performed a maximal cycle test to assess aerobic capacity (V̇o2max). Subjects had a resting vastus lateralis muscle biopsy to assess oxidative enzymes (citrate synthase and βHAD) and molecular (mRNA) targets associated with mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam)]. The octogenarian athletes had a higher ( P < 0.05) absolute (2.6 ± 0.1 vs. 1.6 ± 0.1 l/min) and relative (38 ± 1 vs. 21 ± 1 ml·kg−1·min−1) V̇o2max, ventilation (79 ± 3 vs. 64 ± 7 l/min), heart rate (160 ± 5 vs. 146 ± 8 beats per minute), and final workload (182 ± 4 vs. 131 ± 14 W). Skeletal muscle oxidative enzymes were 54% (citrate synthase) and 42% (βHAD) higher ( P < 0.05) in the octogenarian athletes. Likewise, basal PGC-1α and Tfam mRNA were 135% and 80% greater ( P < 0.05) in the octogenarian athletes. To our knowledge, the V̇o2max of the lifelong endurance athletes is the highest recorded in humans >80 yr of age and comparable to nonendurance trained men 40 years younger. The superior cardiovascular and skeletal muscle health profile of the octogenarian athletes provides a large functional reserve above the aerobic frailty threshold and is associated with lower risk for disability and mortality.

Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems

1994 ◽  
Vol 267 (2) ◽  
pp. R439-R445 ◽  
Author(s):  
C. Leeuwenburgh ◽  
R. Fiebig ◽  
R. Chandwaney ◽  
L. L. Ji
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Vastus Lateralis ◽  
Antioxidant Systems ◽  
Antioxidant Enzyme Activities ◽  
Vastus Lateralis Muscle ◽  
Adult Rats ◽  
Young Rats

Glutathione (GSH) content and antioxidant enzyme activities were investigated in skeletal muscle of young, adult, and old male Fischer 344 rats. Furthermore, the effect of 10 wk of exercise training on these antioxidant systems was evaluated at all ages. In the soleus muscle, GSH concentration increased markedly with age, with no significant change in glutathione disulfide (GSSG) content. Training caused a 30% decrease of GSH (P < 0.05) in the soleus of young rats and a reduction of the GSH-to-GSSG ratio at all ages. Activity of gamma-glutamyl transpeptidase (GGT), a key enzyme for GSH uptake by muscle, was also significantly decreased with training. GSH, GSSG, and the GSH-to-GSSG ratio were not altered with aging or training in the deep portion of vastus lateralis muscle (DVL). Activities of GSH peroxidase (GPX), GSSG reductase (GR), superoxide dismutase (SOD), catalase (CAT), and GSH sulfur-transferase were increased significantly with aging in both soleus and DVL. In DVL, training increased GPX and SOD activities in the young rats, whereas in soleus, training decreased GR and CAT activities in the adult rats and GGT and CAT activities in the old rats. Muscle lipid peroxidation was significantly increased with aging in both DVL and soleus but was not affected by training. These data indicate that aging may cause not only an overall elevation of antioxidant enzyme activities but also a fiber-specific adaptation of GSH system in skeletal muscle. Exercise training, although increasing selective antioxidant enzymes in the young rats, does not offer additional protection against oxidative stress in the senescent muscle.

Fiber hypertrophy and increased oxidative capacity can occur simultaneously in pig glycolytic skeletal muscle

2014 ◽  
Vol 306 (4) ◽  
pp. C354-C363 ◽  
Author(s):  
T. L. Scheffler ◽  
J. M. Scheffler ◽  
S. Park ◽  
S. C. Kasten ◽  
Y. Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Oxidative Capacity ◽  
Mitochondrial Proteins ◽  
Cross Sectional ◽  
Pig Muscle ◽  
Ryanodine Receptor 1 ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Amp Activated Protein Kinase

An inverse relationship between skeletal muscle fiber cross-sectional area (CSA) and oxidative capacity suggests that muscle fibers hypertrophy at the expense of oxidative capacity. Therefore, our objective was to utilize pigs possessing mutations associated with increased oxidative capacity [AMP-activated protein kinase (AMPKγ3R200Q)] or fiber hypertrophy [ryanodine receptor 1 (RyR1R615C)] to determine if these events occur in parallel. Longissimus muscle was collected from wild-type (control), AMPKγ3R200Q, RyR1R615C, and AMPKγ3R200Q-RyR1R615Cpigs. Regardless of AMPK genotype, RyRR615Cincreased fiber CSA by 35%. In contrast, AMPKγ3R200Qpig muscle exhibited greater citrate synthase and β-hydroxyacyl CoA dehydrogenase activity. Isolated mitochondria from AMPKγ3R200Qmuscle had greater maximal, ADP-stimulated oxygen consumption rate. Additionally, AMPKγ3R200Qmuscle contained more (∼50%) of the mitochondrial proteins succinate dehydrogenase and cytochrome c oxidase and more mitochondrial DNA. Surprisingly, RyR1R615Cincreased mitochondrial proteins and DNA, but this was not associated with improved oxidative capacity, suggesting that altered energy metabolism in RyR1R615Cmuscle influences mitochondrial proliferation and protein turnover. Thus pigs that possess both AMPKγ3R200Qand RyRR615Cexhibit increased muscle fiber CSA as well as greater oxidative capacity. Together, our findings support the notion that hypertrophy and enhanced oxidative capacity can occur simultaneously in skeletal muscle and suggest that the signaling mechanisms controlling these events are independently regulated.

scholarly journals Cytoskeletal structure of skeletal muscle: identification of an intricate exosarcomeric microtubule lattice in slow- and fast-twitch muscle fibers.

1993 ◽  
Vol 41 (7) ◽  
pp. 1013-1021 ◽  
Author(s):  
S Boudriau ◽  
M Vincent ◽  
C H Côté ◽  
P A Rogers
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Vastus Lateralis ◽  
Muscle Fiber Types ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Fiber Types ◽  
Mammalian Skeletal Muscle ◽  
Microtubule Network ◽  
Fast Twitch

We used immunochemical quantification and indirect immunofluorescence to investigate the cell content, distribution, and organization of microtubules in adult rat slow-twitch soleus and fast-twitch vastus lateralis muscles. An immunoblotting assay demonstrated that the soleus muscle (primarily Type I fibers) was found to have a 1.7-fold higher relative content of alpha-tubulin compared with the superficial portion of the vastus lateralis muscle (primarily Type IIb fibers). Both physiological muscle types revealed a complex arrangement of microtubules which displayed oblique, longitudinal, and transverse orientations within the sarcoplasmic space. The predominance of any one particular orientation varied significantly from one muscle tissue section to another. Nuclei were completely surrounded by a dense net-like structure of microtubules. Both muscle fiber types were found to possess a higher density of microtubules in the subsarcolemmal region. These microtubules followed the contour of the sarcolemma in slightly contracted fibers and showed a fine punctate appearance indicative of a restricted distribution. The immunofluorescence results indicate that microtubules are associated with the sarcolemma and therefore may form a part of the membrane cytoskeletal domain of the muscle fiber. We conclude that the microtubule network of the adult mammalian skeletal muscle fiber constitutes a bone fide component of the exosarcomeric cytoskeletal lattice domain along with the intermediate filaments, and as such could therefore participate in the mechanical integration of the various organelles of the myofibers during the contraction-relaxation cycle.

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