PPARGC1A rs8192678 and NRF1 rs6949152 Polymorphisms Are Associated with Muscle Fiber Composition in Women

PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms have been associated with endurance athlete status, endurance performance phenotypes, and certain health-related markers of different pathologies such as metabolic syndrome, diabetes, and dyslipidemia. We hypothesized that they could be considered interesting candidates for explaining inter-individual variations in muscle fiber composition in humans. We aimed to examine possible associations of these polymorphisms with myosin heavy-chain (MHC) isoforms as markers of muscle fiber compositions in vastus lateralis muscle in a population of 214 healthy Japanese subjects, aged between 19 and 79 years. No significant associations were found in men for any measured variables. In contrast, in women, the PPARGC1A rs8192678 A/A genotype was significantly associated with a higher proportion of MHC-I (p = 0.042) and with a lower proportion of MHC-IIx (p = 0.033), and the NRF1 rs6949152 AA genotype was significantly associated with a higher proportion of MHC-I (p = 0.008) and with a lower proportion of MHC IIx (p = 0.035). In women, the genotype scores of the modes presenting the most significant results for PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms were significantly associated with MHC-I (p = 0.0007) and MHC IIx (p = 0.0016). That is, women with combined PPARGC1A A/A and NRF1 A/A genotypes presented the highest proportion of MHC-I and the lowest proportion of MHC-IIx, in contrast to women with combined PPARGC1A GG+GA and NRF1 AG+GG genotypes, who presented the lowest proportion of MHC-I and the highest proportion of MHC-IIx. Our results suggest possible associations between these polymorphisms (both individually and in combination) and the inter-individual variability observed in muscle fiber composition in women, but not in men.

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Short-Term Training, Muscle Glycogen, and Cycle Endurance

Canadian Journal of Applied Physiology ◽

10.1139/h95-024 ◽

1995 ◽

Vol 20 (3) ◽

pp. 315-324 ◽

Cited By ~ 12

Author(s):

Howard J. Green ◽

Marg Ball-Burnett ◽

Steve Symon ◽

Sue Grant ◽

Greg Jamieson

Keyword(s):

Vastus Lateralis ◽

Endurance Performance ◽

Control Group ◽

Vastus Lateralis Muscle ◽

Short Term ◽

Exercise Time ◽

Glycogen Concentration ◽

Prolonged Fatigue ◽

Performance Adaptation ◽

Cycle Endurance

The objective of this study was to test the hypothesis that the increased glycogen concentration found in the working muscles following short-term training would result in an increase in endurance performance. Endurance performance was examined in 8 active but untrained males who cycled until fatigue at 65% [Formula: see text]max prior to and following 3 consecutive days of training. Training consisted of cycling for 2 hrs a day at the same power output used in the prolonged fatigue trials. A 39% increase in cycle time, from 103 ± 7.7 to 143 ± 14 min (p < 0.05), was observed following training. At fatigue prior to training, glycogen concentration in the vastus lateralis muscle was depleted by 75% (317 ± 17 to 78.8 ± 32 mmol∙glucosyl units∙kg−1 d.w). Following training, glycogen concentration at a comparable work time was 2.3 times higher. The elevated glycogen level following training was due both to higher glycogen at rest and during exercise. The energy cost of the activity as measured by the [Formula: see text] at selected intervals was unchanged with training. No change (p > 0.05) in exercise time was observed in a control group who were subjected to similar exercise protocols approximately 1 to 2 weeks apart. It is concluded that short-term training at least in untrained individuals ([Formula: see text]max averaging 43.6 ± 2.9 ml∙kg−1∙min−1) substantially elevates submaximal exercise tolerance and that the increase in resistance to fatigue is related to the elevated availability of glycogen. Key words: endurance performance, adaptation, carbohydrate, vastus lateralis

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Effect of Eccentric and Concentric Contraction Mode on Myogenic Regulatory Factors Expression in Human Vastus Lateralis Muscle

10.21203/rs.3.rs-800966/v1 ◽

2021 ◽

Author(s):

Mostafa Sabouri ◽

Pejman Taghibeikzadehbadr ◽

Fatemeh Shabkhiz ◽

Zahra Izanloo ◽

Farahnaz Amir Shaghaghi

Keyword(s):

Vastus Lateralis ◽

Vastus Lateralis Muscle ◽

Myogenic Regulatory Factors ◽

Mhc I ◽

Regulatory Factors ◽

Isokinetic Contraction ◽

Concentric Contraction ◽

Significant Difference ◽

Lateralis Muscle ◽

Mhc Iia

Abstract Background: Skeletal muscle contractions are caused to release myokines by muscle fiber. This study investigated the myogenic regulatory factors, as MHC I, IIA, IIX, Myo-D, MRF4, Murf, Atrogin-1, Decorin, Myonection, and IL-15 mRNA expression in the response of eccentric vs. concentric contraction. Methods: Eighteen healthy men were randomly divided into two eccentric and concentric groups, each of 9 persons. Isokinetic contraction protocols included maximal single-leg eccentric or concentric knee extension tasks at 60°/s with the dominant leg. Contractions consisted of a maximum of 12 sets of 10 reps, and the rest time between each set was 30 seconds. The baseline biopsy was performed four weeks before the study, and post-test biopsies were taken immediately after exercise protocols from Vastus Lateralis muscle. The gene expression levels evaluated using Real-Time PCR methods. Results: A significant difference in MyoD, MRF4, Myonection, and Decorin mRNA, were observed following eccentric or concentric contractions (P≤0.05). The MHC I, MHC IIA, IL-15 mRNA has been changed significantly compared to the pre-exercise in the concentric group (P≤0.05). While only MHC IIX and Atrogin-1 mRNA changed significantly in the eccentric group (P≤0.05). Additionally, the results showed a significant difference in MyoD, MRF4, IL-15, and Decorin were observed at the follow-up values between eccentric or concentric groups (P≤0.05). Conclusion: Our findings highlight the growing importance of elucidating the different responses of muscle growth factors associated with a myogenic activity such as MHC IIA, Decorin, IL-15, Myonectin, Decorin, MuRF1, and MHC IIX mRNA in following to various types of exercise.

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Effect of resistance training on single muscle fiber contractile function in older men

Journal of Applied Physiology ◽

10.1152/jappl.2000.89.1.143 ◽

2000 ◽

Vol 89 (1) ◽

pp. 143-152 ◽

Cited By ~ 174

Author(s):

Scott Trappe ◽

David Williamson ◽

Michael Godard ◽

David Porter ◽

Greg Rowden ◽

...

Keyword(s):

Resistance Training ◽

Muscle Fiber ◽

Contractile Function ◽

Vastus Lateralis ◽

Muscle Fibers ◽

Older Men ◽

Single Muscle ◽

Mhc I ◽

Before And After ◽

Mhc Iia

The purpose of this study was to examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older men ( n = 7; age = 74 ± 2 yr and weight = 75 ± 5 kg). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsy samples were obtained from the vastus lateralis before and after PRT (pre- and post-PRT, respectively). For analysis, chemically skinned single muscle fibers were studied at 15°C for peak tension [the maximal isometric force (Po)], unloaded shortening velocity ( V o), and force-velocity parameters. In this study, a total of 199 (89 pre- and 110 post-PRT) myosin heavy chain (MHC) I and 99 (55 pre- and 44 post-PRT) MHC IIa fibers were reported. Because of the minimal number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 20% (83 ± 1 to 100 ± 1 μm) and 13% (86 ± 1 to 97 ± 2 μm) in MHC I and IIa fibers, respectively ( P < 0.05). Po was higher ( P < 0.05) in MHC I (0.58 ± 0.02 to 0.90 ± 0.02 mN) and IIa (0.68 ± 0.02 to 0.85 ± 0.03 mN) fibers. Muscle fiber V o was elevated 75% (MHC I) and 45% (MHC IIa) after PRT ( P < 0.05). MHC I and IIa fiber power increased ( P < 0.05) from 7.7 ± 0.5 to 17.6 ± 0.9 μN · fiber lengths · s−1 and from 25.5 to 41.1 μN · fiber lengths · s−1, respectively. These data indicate that PRT in elderly men increases muscle cell size, strength, contractile velocity, and power in both slow- and fast-twitch muscle fibers. However, it appears that these changes are more pronounced in the MHC I muscle fibers.

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Effects of weight loss and leptin on skeletal muscle in human subjects

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00397.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. R1259-R1266 ◽

Cited By ~ 25

Author(s):

Kenneth M. Baldwin ◽

Denis R. Joanisse ◽

Fadia Haddad ◽

Rochelle L. Goldsmith ◽

Dympna Gallagher ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Body Weight ◽

Human Subjects ◽

Vastus Lateralis ◽

Vastus Lateralis Muscle ◽

Work Efficiency ◽

Mhc I ◽

Reduced Body ◽

Lateralis Muscle

Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform. We performed analyses of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle metabolic properties as well as mRNA expression of different isoforms of the MHC and sarcoplasmic endoplasmic reticular Ca2+-dependent ATPase (SERCA) in subjects studied before weight loss and then again after losing 10% of their initial weight and receiving twice daily injections of either placebo or replacement leptin in a single blind crossover design. We found that the maintenance of a reduced body weight was associated with significant increases in the relative gene expression of MHC I mRNA that was reversed by the administration of leptin as well as an increase in the expression of SERCA2 that was not significantly affected by leptin. Leptin administration also resulted in a significant increase in the expression of the less MHC IIx isoform compared with subjects receiving placebo. These findings are consistent with the leptin-reversible increase in skeletal muscle chemomechanical work efficiency and decrease in the ratio of glycolytic/oxidative enzyme activities observed in subjects following dietary weight loss.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00557.2014 ◽

2015 ◽

Vol 118 (8) ◽

pp. 1040-1049 ◽

Cited By ~ 16

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.

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Role of selected polymorphisms in determining muscle fiber composition in Japanese men and women

Journal of Applied Physiology ◽

10.1152/japplphysiol.00953.2017 ◽

2018 ◽

Vol 124 (5) ◽

pp. 1377-1384 ◽

Cited By ~ 4

Author(s):

Hiroshi Kumagai ◽

Takuro Tobina ◽

Noriko Ichinoseki-Sekine ◽

Ryo Kakigi ◽

Takamasa Tsuzuki ◽

...

Keyword(s):

Sex Differences ◽

Genetic Polymorphisms ◽

Muscle Fiber ◽

Angiotensin Converting Enzyme Gene ◽

Converting Enzyme ◽

Japanese Men ◽

Mhc I ◽

Enzyme Gene ◽

Fiber Composition ◽

Mhc Iia

Genetic polymorphisms and sex differences are suggested to affect muscle fiber composition; however, no study has investigated the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences. Therefore, the present study examined the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences in the Japanese population. The present study included 211 healthy Japanese individuals (102 men and 109 women). Muscle biopsies were obtained from the vastus lateralis to determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx). Moreover, we analyzed polymorphisms in α-actinin-3 gene ( ACTN3; rs1815739 ), angiotensin-converting enzyme gene ( ACE; rs4341 ), hypoxia-inducible factor 1 α gene ( rs11549465 ), vascular endothelial growth factor receptor 2 gene ( rs1870377 ), and angiotensin II receptor, type 2 gene ( rs11091046 ), by TaqMan single-nucleotide polymorphism genotyping assays. The proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%, respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID + DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE insertion/deletion (I/D) was significantly correlated with the proportion of MHC-I ( r = −0.23) and MHC-IIx ( r = 0.27) in men. In contrast, no significant correlation was observed between the examined polymorphisms and muscle fiber composition in women. These results suggest that the ACTN3 R577X and ACE I/D polymorphisms independently affect the proportion of human skeletal muscle fibers MHC-I and MHC-IIx in men but not in women.NEW & NOTEWORTHY In men, the RR + RX genotype of the α-actinin-3 gene ( ACTN3) R577X polymorphism was associated with a higher proportion of myosin heavy chain (MHC)-IIx. The ID + DD genotype of the angiotensin-converting enzyme gene ( ACE) insertion/deletion (I/D) polymorphism, in contrast to a previous finding, was associated with a higher proportion of MHC-I in men. In addition, the combined genotype of these polymorphisms was correlated with the proportion of MHC-I and MHC-IIx in men. Thus ACTN3 R577X and ACE I/D polymorphisms influence the muscle fiber composition in Japanese men.

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Concurrent aerobic exercise interferes with the satellite cell response to acute resistance exercise

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00035.2012 ◽

2012 ◽

Vol 302 (12) ◽

pp. R1458-R1465 ◽

Cited By ~ 17

Author(s):

Lyle Babcock ◽

Matthew Escano ◽

Andrew D'Lugos ◽

Kent Todd ◽

Kevin Murach ◽

...

Keyword(s):

Resistance Exercise ◽

Aerobic Exercise ◽

Satellite Cell ◽

Muscle Fiber ◽

Fiber Type ◽

Vastus Lateralis ◽

Muscle Adaptation ◽

Mhc I ◽

Fiber Growth ◽

Concurrent Exercise

The addition of aerobic exercise (AE) to a resistance exercise (RE) program (concurrent exercise, CE) can interfere with maximum muscle fiber growth achieved with RE. Further, CE appears to markedly affect the growth of myosin heavy chain (MHC) I, but not MHC IIa fibers. The mechanism responsible for this “interference” is unclear. Satellite cell (SC) responsiveness to exercise appears to influence muscle adaptation but has not yet been examined following acute concurrent exercise. Thus, we assessed the fiber-type-specific SC response to RE, AE, and CE exercise. Eight college-aged males completed the following two exercise trials: the RE trial, which consisted of unilateral leg extensions and presses (4 sets ≥ 10 repetitions: 75% 1 repetition maximum, RM); and the AE/CE trial, which included an identical RE protocol with the opposite leg, immediately followed by subjects cycling for 90 min (60% Wmax). Muscle biopsies were obtained from the vastus lateralis before and 4 days after each session. Samples were cross-sectioned, stained with antibodies against NCAM, Ki-67, and MHC I, counterstained with DAPI, and analyzed for SC density (SC per fiber), SC activation, and fiber type. SC density increased to a greater extent following RE (38 ± 10%), compared with CE (−6 ± 8%). Similarly, MHC I muscle fiber SC density displayed a greater increase following RE (46 ± 14%), compared with AE (−7 ± 17%) and CE (−8 ± 8%). Our data indicate that the SC response to RE is blunted when immediately followed by AE, at least in MHC I muscle fibers, and possibly MHC II fibers. This suggests that the physiological environment evoked by AE might attenuate the eventual addition of myonuclei important for maximum muscle fiber growth and consequent force-producing capacity.

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Reduction in hybrid single muscle fiber proportions with resistance training in humans

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.5.1955 ◽

2001 ◽

Vol 91 (5) ◽

pp. 1955-1961 ◽

Cited By ~ 97

Author(s):

D. L. Williamson ◽

P. M. Gallagher ◽

C. C. Carroll ◽

U. Raue ◽

S. W. Trappe

Keyword(s):

Resistance Training ◽

Muscle Fiber ◽

Vastus Lateralis ◽

Electrophoretic Analysis ◽

Training Data ◽

Single Muscle ◽

Hybrid Fibers ◽

Mhc I ◽

Single Muscle Fiber ◽

Mhc Iia

The purpose of this investigation was to examine the effects of 12 wk of progressive resistance training (PRT) on single muscle fiber myosin heavy chain (MHC; I, I/IIa, I/IIa/IIx, IIa, IIa/IIx, IIx) isoform proportions in young individuals. Young, untrained men (YM; n = 6) and women (YW; n = 6) (age = 22 ± 1 and 25 ± 2 yr for YW and YM, respectively) received pre- and post-PRT muscle biopsies from the right vastus lateralis for single muscle fiber MHC distribution by electrophoretic analysis (192 ± 5 pre- and 183 ± 6 post-fibers/subject analyzed; 4,495 fibers total). Data are presented as percentages of the total fibers analyzed per subject. The PRT protocol elicited an increase in the pure MHC IIa (Δ = + 24 and + 27; YW and YM, respectively; P < 0.05) with no change in the pure MHC I distribution. The hybrid MHC distributions decreased I/IIa/IIx (Δ = −2; YM and YW; P < 0.05), IIa/IIx (Δ = −13 and −19 for YM and YW, respectively; P < 0.05), and total hybrid fiber proportion (I/IIa + I/IIa/IIx + IIa/IIx) decreased (Δ = −19 and −30 for YM and YW, respectively; P < 0.05) with the training, as did the MHC IIx distribution (Δ = −2; YW only; P < 0.05). Alterations in the predominance of MHC isoforms within hybrid fibers (decrease in MHC I-dominant I/IIa and nondominant MHC IIa/IIx, increase in MHC IIa-dominant IIa/IIx; P < 0.05) appeared to contribute to the increase in the MHC IIa proportion. Electrophoresis of muscle cross sections revealed an ∼7% increase ( P< 0.05) in MHC IIa proportion in both groups, whereas the MHC IIx decrease by 7.5 and 11.6% post-PRT in YW and YM, respectively. MHC I proportions increase in YM by 4.8% ( P < 0.05) post-PRT. These findings further support previous resistance training data in young adults with respect to the increase in the MHC IIa proportions but demonstrate that a majority of the change can be attributed to the decrease in single-fiber hybrid proportions.

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

Journal of Histochemistry & Cytochemistry ◽

10.1177/41.7.8515044 ◽

1993 ◽

Vol 41 (7) ◽

pp. 1013-1021 ◽

Cited By ~ 25

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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