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The Time Course for Elevated Muscle Protein Synthesis Following Heavy Resistance Exercise



It has been shown that muscle protein synthetic rate (MPS) is elevated in humans by 50% at 4 hrs following a bout of heavy resistance training, and by 109% at 24 hrs following training. This study further examined the time course for elevated muscle protein synthesis by examining its rate at 36 hrs following a training session. Six healthy young men performed 12 sets of 6- to 12-RM elbow flexion exercises with one arm while the opposite arm served as a control. MPS was calculated from the in vivo rate of incorporation of L-[1,2-13C2] leucine into biceps brachii of both arms using the primed constant infusion technique over 11 hrs. At an average time of 36 hrs postexercise, MPS in the exercised arm had returned to within 14% of the control arm value, the difference being nonsignificant. It is concluded that following a bout of heavy resistance training, MPS increases rapidly, is more than double at 24 hrs, and thereafter declines rapidly so that at 36 hrs it has almost returned to baseline.
The Time Course for Elevated Muscle Protein
Synthesis Following Heavy Resistance Exercise
J. Duncan MacDougall, Martin J. Gibala, Mark
MacDonald, Stephen
Interisano, and Kevin
Catalogue Data
MacDougall, J.D., Gibala, M.J., Tarnopolsky, M.A., MacDonald, J.R., Interisano, S.A.,
and Yarasheski, K.E. (1995). The time course for elevated muscle protein synthesis
following heavy resistance exercise.
Appl. Physiol.
20(4): 480-486.
Canadian Society for Exercise Physiology.
L-[-I3C] leucine, muscle hypertrophy, training frequency, mass spectrometry
leucine L-[-I3C], hypertrophie musculaire, frhquence d'entrainement, spec-
tromPtre de masse
It has been shown that muscle protein synthetic rate (MPS) is elevated in humans by 50%
at 4 hrs following a bout of heavy resistance training, and by 109% at 24 hrs following
training. This study further examined the time course for elevated muscle protein synthesis
by examining its rate at
hrs following a training session. Six healthy young men
performed 12 sets of
to 12-RM elbow flexion exercises with one arm while the opposite
arm served as a control. MPS was calculated from the in vivo rate of incorporation of
L-[l ,2-13C2] leucine into biceps brachii of both arms using the primed constant infusion
technique over 11 hrs. At an average time of
hrs postexercise, MPS in the exercised arm
had returned to within 14% of the control arm value, the diflerence being nonsigniJicant. It
is concluded that following a bout of heavy resistance training, MPS increases rapidly,
is more than double at 24 hrs, and thereafter declines rapidly so that at
hrs it has
almost returned to baseline.
On a dhja montrh que le taux de synthbe de prothine musculaire (SPM) est hlevh duns
l'homme de 50% a 4 h apris une seance d'entrainement et de 109% a 24 h apt-t?s
l'entrainement. La prhsente htude continue l'examen du c-ours temporel de la synthese
MacDougall, Gibala, Tarnopolsky, MacDonald, and Interisano: Department of
Kinesiology, McMaster University, Hamilton, Ontario L8S 4Kl; Yarasheski: Metabolism
Division, Washington University School of Medicine, St. Louis, MO 631 10, USA.
Can. J. Appl. Physiol. 1995.20:480-486.
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Protein Synthesis Following Exercise
klevke de protkine en examinant le faux
36 h aprts une skance d'entrainement. Six
jeunes hommes en bonne santt! ont effectut! un total de 12 skries de 6- 12-RM d'exercices
de flexion du coude avec un seul bras, l'autre agissant comme tkmoin. Nous avons calcuM
la SPM
partir de l'enrichissement du leucine L-[l ,2-'3C2] duns des biopsies du biceps
brachii prilevkes des deux bras en employant la technique d'infusion constant amorck
pendant 11 h.
36 h en moyen aprts I'entrainement, la SPM du bras travaillk s'ktait
rendue jusqu'a moins de 14% de la valeur du bras tkmoin, la divergence e'tant non
significative. On conclut que la SPM accroit rapidement aprts une skance d'entrainement
de rbistance lourde, qu'elle atteint sa valeur
24 h, et qu'elle dkcroit rapidement
subskquemment, regagnant a peu prts sa valeur initiale
36 h.
We have previously shown that the biceps brachii mixed muscle protein synthetic
rate (MPS) is elevated in experienced weight trainers by 50% approximately
4 hrs after training, and by 109% approximately 24 hrs after training (Chesley
et al., 1992; MacDougall et al., 1992). The present study further investigated the
time course for elevated protein synthesis by examining its rate at approximately
36 hrs following a training session.
As in our previous study (Chesley et al., 1992), MPS was measured in biceps
brachii following an acute bout of heavy resistance exercise by the elbow flexors
of one arm so that the opposite arm served as a control. Since the duration that
protein synthesis might remain elevated in the exercised arm was unknown, our
original plan was to examine MPS 36 hrs following training and then at subsequent
12-hr intervals until MPS returned to that of the control arm.
Six healthy young men (23
1.7 yrs) who regularly engaged in heavy resistance
(bodybuilding) training served as subjects. They did not differ from our previous
subjects as to age, height, body weight, or training experience. They were advised
of the risks associated with the study, in accordance with the university's human
ethics committee, and provided written informed consent.
Subjects refrained from resistance exercise training for 3 days. At approxi-
mately 7 p.m. on the evening of the 4th day, they performed a typical training
session for the elbow flexors of one randomly chosen arm. As in our previous
study, the session was supervised by a coinvestigator and consisted of 4 sets of
single arm biceps, concentration and preacher curls at 80% of maximum
so that a total of 12 sets was completed in all. Each set was undertaken to
muscular "failure" and a rest period of 3 to 4 min was provided between sets.
The young men were instructed to consume their normal breakfast and lunch the
following day and to report back to the laboratory at 5 p.m. to consume a standard
meal. The energy content of the meal was 1,200 Kcal and consisted of 70%
carbohydrate, 16% protein, and 14% fat. Two hours later a 20-Ga catheter was
inserted into a hand vein for blood sampling and a second catheter was positioned
in a contralateral forearm vein for isotope tracer infusion. Subjects read or watched
Can. J. Appl. Physiol. 1995.20:480-486.
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482 MacDougall, Gibala, Tarnopolsky, et al.
movies until their normal bedtime and slept in the laboratory overnight. The rate
of tracer incorporation into biceps brachii was measured in both arms between
8 p.m. that night and 7 a.m. the following morning so that the midpoint would
hrs after their previous training session.
The in vivo rate of MPS was determined from the enrichment of L-[1,2-"C2]
leucine in biopsy samples using an 1 1-hr primed constant intravenous infusion. A
priming dose of L-[l ,2-I3C2] leucine (>99% isotopic purity, Tracer Technologies,
Somerville, MA) was administered (7.58 pmol
kg-'), followed by a constant
infusion (7.58 pmol
h-I) for 12.5 hrs using a Harvard syringe pump.
Arterialized blood samples (hot box at 65°C) were taken prior to infusion and
at 1.5, 10.5, 11.5, 12, and 12.5 hrs for determination of plasma [1,2-I3C2]
a-ketoisocaproic acid (a-KIC). Needle biopsies were taken from biceps brachii
of both arms 90 min following the priming dose and 11 hrs later.
Enrichment of plasma [l ,2-l3C2]
a-KIC (atom
excess) was determined
by electron impact ionization gas chromatography-mass spectrometry (Hewlett-
Packard 5980A-MSD), as has been previously described (Tarnopolsky et al.,
1991). Enrichment of muscle [I ,2-"C2] leucine (mole
excess) was determined
by capillary gas
isotope-ratio mass spectroscopy as
described by Yarasheski et al. (1992). MPS was calculated for each sample
according to the method of Nair et al. (1988) using plasma [1,2-'"2]
as the precursor pool enrichment, as we have previously detailed (MacDougall
et al., 1992). Data are expressed as
hr-I, where the incorporation time is the
time between biopsies for each subject. Differences in MPS between control and
exercised arms and possible changes in plasma [l,2-13C2]
a-KIC during the
infusion procedure were assessed by analysis of variance.
Enrichment for plasma [l,2-'3C2]
a-KIC at each sampling time is shown in
Table 1. Each sample was analyzed in duplicate and the intra-assay coefficient
of variation was 0.82%. Although there was a tendency for enrichments to decline
slightly toward the end of the infusion period, this was not statistically significant.
Plasma enrichments were remarkably consistent between the 1.5- and 10.5-hr
Enrichment (atom
Sampling time
1.5 hrs 10.5 hrs
1.5 hrs 12.0 hrs 12.5 hrs
Differences are not statistically significant.
Can. J. Appl. Physiol. 1995.20:480-486.
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Protein Synthesis Following Exercise 483
points, which represented the major portion of the time (9 1
over which MPS
was measured.
MPS for both control and exercised arms are illustrated in Figure 1. Dupli-
cate analysis for enrichment of muscle protein
,2-"C2] leucine were performed
on each sample and the intra-assay coefficient of variation was 2.66%. Although
MPS was approximately 14% higher in the exercised arm than in the control
arm, this difference was not statistically significant.
MPS in the control arms (0.0408 f0.0103% hr-2) was similar to the mean
value of 0.0538 (f0.0148% hr-I) which we found in the control arms in our
previous study (Chesley et al., 1992). The results of the present study have been
combined with our previous data to illustrate MPS at 4, 24, and 36 hrs following
exercise (Figure 2).
Combined data from the subjects in the present study and from the two groups
in our previous study indicate that biceps brachii MPS is elevated by 50, 109,
and 14% at 4, 24, and 36 hrs, respectively, following a bout of heavy resistance
training (Figure 2). Although a single within-group design at the three time points
would have been preferable, we rejected it on ethical grounds because it would
have required a total of six biopsies from biceps of each
We are aware of
the limitations of a between-group design, and for this reason took care to match
our three groups according to age, body size, and training background; we had
them perform the identical exercises at the same volume and intensity.
Rate of muscle protein synthesis in biceps brachii for the control and exer-
cised arms 36 hrs after resistance training.
6, values are means
The differ-
ence between both arms was not statistically significant.
Can. J. Appl. Physiol. 1995.20:480-486.
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MacDougall, Gibala, Tarnopolsky, et al.
Increase in muscle protein synthetic rate
4, 24,
hrs after a single re-
sistance training bout. Values indicate the difference between MPS in the exercised
and control arm. Data at
hrs are from a previous study (see text). "Significant
The method for measuring MPS was modified somewhat from our previous
approach in that we infused doubly labeled (L-[l ,2-'VC,]) leucine and maintained
the constant infusion over 12.5 hrs instead of singly labeled (L-[I-'"]) leucine
over 6 hrs. Our finding in the present study, that MPS in the control
similar to control arm values in the previous study, indicates that the two methods
yield similar results. Moreover, since it is the
in MPS between the
exercised and nonexercised arms that indicates an elevated muscle protein synthe-
sis, possible methodological differences have been controlled for.
It should be recognized that the values reported for MPS at 4 and 24 hrs
represent the average values over the 4 hrs during which MPS was measured.
Similarly, the 36-hr value is the average value over 11 hrs (i.e., between 30.5
and 41.5 hrs after exercise). The assumption in presenting these data at a single
time point is that MPS is linear over the assessment period. This may not of
course be the case. We interpret our finding-that at 36 hrs, MPS in the exercised
arm was not significantly higher than in the control arm (in 4 subjects it was
higher but in 2 subjects it was not)-as indicating that, at this point, MPS was
already returning to its preexercise rate. The relatively large standard error at
this point probably reflects interindividual differences in the rate at which addi-
tional protein synthesis is completed after training. In addition, since MPS at
this point in time was not significantly elevated, we decided that further investiga-
tion at, say, 48 hrs was unnecessary.
Since the elevated MPS following heavy resistance exercise occurs in the
absence of an elevation in
concentration (Chesley et al., 1992), its up-
Can. J. Appl. Physiol. 1995.20:480-486.
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Protein Synthesis Following Exercise 485
regulation appears to be the result of posttranscriptional events (Chesley et al.,
1992; Wong and Booth, 1990). The method we have used is a measure of mixed
muscle protein synthetic rate. The extent to which muscle hypertrophy occurs is
dependent upon
protein synthesis, that is, the difference between protein
synthesis and degradation. It is apparent that the observed increases in MPS are
accompanied by a concomitant increase in muscle protein degradation, or else
muscle size would increase to a much greater extent than is known to occur with
resistance training (MacDougall et al., 1980).
Degradation of muscle protein may to a large extent be due to the mechanical
damage that occurs to contractile protein during heavy resistance exercise. We
have recently documented disruption of muscle fine structure in biceps brachii
following exercise similar to that in the present study and have found that,
24 hrs after exercise, some degree of myofibrillar disruption could be detected
in as many as 80% of the fibres examined with electron microscopy (Gibala et
al., 1995).
Knowledge of the time course for elevated MPS following resistance exer-
cise is important to athletes and professionals in muscle rehabilitation who are
interested in optimum methods for increasing muscle size and strength. Empiri-
cally, one might hypothesize that the most effective training frequency would
be such that the subsequent training session should not occur until the protein
synthesis stimulated by the previous session has returned to its pretraining rate.
If this is true, the present data suggest an optimum recovery time of at least
to 48 hrs between training sessions; however, the time course for changes in
protein degradation is not known.
In summary, the data from the present and our previous study (Chesley et
al., 1992) indicate that when experienced subjects undertake a bout of heavy
resistance training, the protein synthetic rate in the exercised muscle increases
rapidly, is more than double approximately 24 hrs following exercise, and there-
after declines so that at
hrs it is almost back to baseline.
Chesley, A., MacDougall, J.D., Tarnopolsky, M.A., Atkinson, S.A., and Smith, K. (1992).
Changes in human muscle protein synthesis after resistance exercise.
73: 1383- 1388.
Gibala, M.J., MacDougall, J.D., Tarnopolsky, M.A., Stauber, W.T., and Eloriagga, A.
(1995). Changes in human skeletal muscle ultrastructure and force production after
acute resistance exercise.
Appl. Physiol.
78: 702-708.
MacDougall, J.D., Elder, G.C.B., Sale, D.G., Moroz, J.S., and Sutton, J.F.
1980). Effects
of strength training and immobilization on human muscle fibres.
Physiol. Occup. Physiol.
43: 25-34.
MacDougall, J.D., Tarnopolsky, M.A., Chesley, A., and Atkinson, S.A. (1992). Changes
in muscle protein synthesis following heavy resistance exercise in humans: A pilot
Acta Physiol. Scand.
146: 403-404.
Nair, K.S., Halliday, D., and Griggs, R.C. (1988). Leucine incorporation into mixed
skeletal muscle protein in humans.
254: E208-E213.
Tarnopolsky, M.A., Atkinson, S.A., MacDougall, J.D., Senor, B.B., Lemon, P.W.R., and
Schwarcz, H. (1991). Whole body leucine metabolism during and after resistance
exercise in fed humans.
Med. Sci. Sports Exerc.
23: 324-333.
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486 MacDougall, Gibala, Tarnopolsky, et al.
and Booth, F.W. (1990). Protein metabolism in rat tibialis anterior muscle
after stimulated chronic eccentric exercise.
Appl. Physiol.
69: 17 18- 1724.
Yarasheski, K.E., Smith, K., Rennie,
and Bier, D.M. (1992). Measurement of muscle
protein fractional synthetic rate by capillary gas
ratio mass spectrometry.
Biol. Mass Spectr.
21: 486-490.
This study was supported by the Natural Sciences and Engineering Research Council of
Canada and by a Mass Spectrometry Research Grant (NIH-RR 00954).
The authors acknowledge the technical assistance of Brian Roy and Barbara Wilhelm and
the secretarial assistance of Mary Cleland.
Received March
1995; accepted in final form July 31, 1995.
Can. J. Appl. Physiol. 1995.20:480-486.
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... RE increases overall protein turnover by concomitantly increasing the rates of both MPS and MPB. Following a single bout of RE, the rate of MPS is increased above rest in the early recovery period (e.g., 1-5 h) [1][2][3] through at least 24 h [1,2] and up to 48 h [2] after exercise. Increases up to 2.7-fold have been reported [1][2][3]. ...
... RE increases overall protein turnover by concomitantly increasing the rates of both MPS and MPB. Following a single bout of RE, the rate of MPS is increased above rest in the early recovery period (e.g., 1-5 h) [1][2][3] through at least 24 h [1,2] and up to 48 h [2] after exercise. Increases up to 2.7-fold have been reported [1][2][3]. ...
... Following a single bout of RE, the rate of MPS is increased above rest in the early recovery period (e.g., 1-5 h) [1][2][3] through at least 24 h [1,2] and up to 48 h [2] after exercise. Increases up to 2.7-fold have been reported [1][2][3]. Provided sufficient mechanical stimulation and nutrient intake, the increase in MPS exceeds that of MPB, resulting in net protein accretion [2,4,5], with MPS measured using primed constant infusions of [ 2 H 5 ]phenylalanine [2,4,5] and MPB measured using a primed constant infusion of 15N-phenylalanine [2] or phenylalanine rate of appearance in circulation [4,5]. This demonstrates that muscle hypertrophy associated with RE training is due to greater elevation in MPS than in MPB and not suppression of MPB. ...
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Skeletal muscle mass is determined by the balance between muscle protein synthesis (MPS) and degradation. Several intracellular signaling pathways control this balance, including mammalian/mechanistic target of rapamycin (mTOR) complex 1 (C1). Activation of this pathway in skeletal muscle is controlled, in part, by nutrition (e.g., amino acids and alcohol) and exercise (e.g., resistance exercise (RE)). Acute and chronic alcohol use can result in myopathy, and evidence points to altered mTORC1 signaling as a contributing factor. Moreover, individuals who regularly perform RE or vigorous aerobic exercise are more likely to use alcohol frequently and in larger quantities. Therefore, alcohol may antagonize beneficial exercise-induced increases in mTORC1 pathway signaling. The purpose of this review is to synthesize up-to-date evidence regarding mTORC1 pathway signaling and the independent and combined effects of acute alcohol and RE on activation of the mTORC1 pathway. Overall, acute alcohol impairs and RE activates mTORC1 pathway signaling; however, effects vary by model, sex, feeding, training status, quantity, etc., such that anabolic stimuli may partially rescue the alcohol-mediated pathway inhibition. Likewise, the impact of alcohol on RE-induced mTORC1 pathway signaling appears dependent on several factors including nutrition and sex, although many questions remain unanswered. Accordingly, we identify gaps in the literature that remain to be elucidated to fully understand the independent and combined impacts of alcohol and RE on mTORC1 pathway signaling.
... In this regard, the significant changes in body composition variables describing skeletal muscle mass, appendicular skeletal muscle mass and body cell mass should be viewed as strictly related to the observed changes in cellular water compartmentalization rather than as a result of muscle protein synthesis (MPS), which is not expected after only few days, although quite intensive, of physical activity. Sustained resistive exercise targeting muscles over several weeks is, in fact, needed to induce cumulative periods of positive net protein balance, which requires that the rate of MPS exceeds the rate of muscle protein breakdown (MacDougall et al. 1995;Phillips et al. 1997). Before MPS-related muscle growth takes place, muscles can appear larger following acute training due to sarcoplasmic hypertrophy. ...
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Purpose To evaluate the effects of wild trekking by examining, in postmenopausal women, the physiological adaptations to an intensive 5-day wild trek and comparing their responses to those displayed by a group of men of comparable age, training status and mountaineering skills. Methods Six healthy, active postmenopausal women in their sixth decade of life participated in the study. Six men of comparable age and training status were also enrolled for gender-based comparisons. The participants traversed the Selvaggio Blu wild trek (Sardinia, Italy) completing a total of 56 km, for an overall height differential of 14,301 m. During all 5-day trek, subjects were supervised by two alpine guides. Changes in body composition, cardiorespiratory fitness, and metabolic patterns of energy expenditure were evaluated before and after the intervention. Results Total energy expenditure during the trek was significantly higher (p = 0.03) in women (12.88 ± 3.37 kcal/h/kg) than men (9.27 ± 0.89 kcal/h/kg). Extracellular (ECW) and intracellular water (ICW) increased significantly following the trek only in women (ECW: − 3.8%; p = 0.01; ICW: + 3.4%; p = 0.01). The same applied to fat-free mass (+ 5.6%; p = 0.006), fat mass (− 20.4%; p = 0.006), skeletal muscle mass (+ 9.5%; p = 0.007), and appendicular muscle mass (+ 7.3%; p = 0.002). Peak VO2/kg (+ 9.4%; p = 0.05) and fat oxidation (at 80 W: + 26.96%; p = 0.04; at 100 W: + 40.95%; p = 0.02; at 120 W: + 83.02%; p = 0.01) were found increased only in women, although no concurrent changes in partial pressure of end-tidal CO2 (PETCO2) was observed. Conclusions In postmenopausal women, a 5-day, intensive and physically/technically demanding outdoor trekking activity led to significant and potentially relevant changes in body composition, energy balance and metabolism that are generally attained following quite longer periods of training.
... Changes in mRNA during and following exercise are transient, and research in model systems has shown that the relationship between changes in mRNA and protein is timedependent (see Figure 3A; [44]). The timing of muscle/tissue sampling is, therefore, a critical methodological issue that directly impacts the magnitude of the observed exercise-induced changes in mRNA [51,53,[65][66][67][68][69][70][71] and likely contributes to the observed discordance between exercise-induced changes in mRNA and training-induced changes in proteins and phenotype [5,48,49,54]. Further research is required to establish a comprehensive time course for changes in mRNA in response to exercise; this time course should also be investigated in different populations (e.g., men, women, young, elderly, physically active, and sedentary) and following different exercise modalities, intensities, frequencies, and durations [62]. ...
... The range of protein requirement in both resistance training [28,30] and endurance athletes [18,31] may be attributed to the measurement conditions related to physical activity, such as no exercise for 48 h [30], after 8 h of exercise [18,28], and after 24 h of exercise [31]. These results have been obtained only in resistance-trained athletes; nonetheless, a single exercise session increases muscle protein synthesis 24 to 48 h later, thereby increasing sensitivity to dietary protein intake [50][51][52]. Therefore, the protein requirements for athletes and persons with high physical activity should be set using the IAAO method after considering various situations including physical activity level, during exercise, and elapsed time after exercising. ...
Background: The indicator amino acid oxidation (IAAO) method has been accepted as an approach to evaluate habitual protein requirements under free-living conditions. Objective: This scoping review reports on literature that evaluated protein requirements in humans using the IAAO methods. Methods: Three databases (PubMed/Medline, Web of Science, and ProQuest) were systematically searched to identify studies that evaluated protein requirements using the IAAO method published in English until June 5, 2023. We evaluated the study quality using previously developed criteria. We extracted the characteristics of the study design and the results of protein requirements. Two reviewers conducted both reviews and quality assessments independently; any differences among them were resolved by consensus or agreement of all team members. Results: We extracted 16 articles targeting children, young adults (including pregnant women, resistance training athletes, endurance training athletes, and team sports), and older adults. For quality assessment, 14 studies were evaluated "strong", but the remaining two were "moderate". These studies were conducted in only three countries and not for all sexes or life stages. The range of the estimated average protein requirements of each life stage were 1.3 g/kg body weight/day for children, 0.87 to 2.1 (0.87 - 0.93 for general young adults, 1.22 - 1.52 for pregnant women, 1.49 - 2.0 for resistance-trained athletes, 1.65 - 2.1 for endurance athletes and 1.2 - 1.41 for team sports athletes) g/kg body weight/day for young adults, and 0.85 to 0.96 g/kg body weight/day for older adults. Conclusions: Protein requirements in 14 studies were higher than the current reference for each sex, life stage and physical activity that are related to protein requirement. In the future, protein requirements of various population including sex, life stage could be assessed using the IAAO methods worldwide.
... It is widely accepted that MPS increases in the post-exercise period (Chesley et al. 1992, Yarasheski et al. 1993, MacDougall et al. 1995 and continues (Dreyer et al. 2006) up to 48 h after exercise (Phillips et al. 1997 Other researchers have shown that the increased phosphorylation of mTOR and S6K1 in the post-exercise period can overcome the inhibitory effects of AMPK on eEF2 (Dreyer et al. 2006). In addition, Drummond et al. demonstrated that rapamycin administration before resistance exercise completely blocked eEF2 (Thr56) phosphorylation during post-exercise recovery, which indicated the influential role of mTORC1 in MSP (Drummond et al. 2009). ...
Skeletal muscle is a flexible and adaptable tissue that strongly responds to exercise training. The skeletal muscle responds to exercise by increasing muscle protein synthesis (MPS) when energy is available. One of protein synthesis’s major rate-limiting and critical regulatory steps is the translation elongation pathway. The process of translation elongation in skeletal muscle is highly regulated. It requires elongation factors that are intensely affected by various physiological stimuli such as exercise and the total available energy of cells. Studies have shown that exercise involves the elongation pathway by numerous signalling pathways. Since the elongation pathway, has been far less studied than the other translation steps, its comprehensive prospect and quantitative understanding remain in the dark. This study highlights the current understanding of the effect of exercise training on the translation elongation pathway focussing on the molecular factors affecting the pathway, including Ca²⁺, AMPK, PKA, mTORC1/P70S6K, MAPKs, and myostatin. We further discussed the mode and volume of exercise training intervention on the translation elongation pathway. • What is the topic of this review? This review summarises the impacts of exercise training on the translation elongation pathway in skeletal muscle focussing on eEF2 and eEF2K. • What advances does it highlight? This review highlights mechanisms and factors that profoundly influence the translation elongation pathway and argues that exercise might modulate the response. This review also combines the experimental observations focussing on the regulation of translation elongation during and after exercise. The findings widen our horizon to the notion of mechanisms involved in muscle protein synthesis (MPS) through translation elongation response to exercise training.
... In our quest to characterize salient exercise response parameters in people with obesity, we acknowledge some limitations to this study and suggest areas for future research. First, we measured protein synthesis between 3.5 and 6.5 h following exercise in an effort to capture peak anabolic response based on prior timecourse studies (Fry et al., 2011;MacDougall et al., 1995). It is possible that the peak anabolic response to exercise fell outside this window in this study, in which case additional biopsy timepoints would be required to more confidently identify the time at which peak muscle protein synthesis occurred. ...
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Obesity is associated with several skeletal muscle impairments which can be improved through an aerobic exercise prescription. The possibility that exercise responsiveness is diminished in people with obesity has been suggested but not well‐studied. The purpose of this study was to investigate how obesity influences acute exercise responsiveness in skeletal muscle and circulating amino metabolites. Non‐obese (NO; n = 19; 10F/9M; BMI = 25.1 ± 2.8 kg/m2) and Obese (O; n = 21; 14F/7M; BMI = 37.3 ± 4.6 kg/m2) adults performed 30 min of single‐leg cycling at 70% of VO2peak. 13C6‐Phenylalanine was administered intravenously for muscle protein synthesis measurements. Serial muscle biopsies (vastus lateralis) were collected before exercise and 3.5‐ and 6.5‐h post‐exercise to measure protein synthesis and gene expression. Targeted plasma metabolomics was used to quantitate amino metabolites before and 30 and 90 min after exercise. The exercise‐induced fold change in mixed muscle protein synthesis trended (p = 0.058) higher in NO (1.28 ± 0.54‐fold) compared to O (0.95 ± 0.42‐fold) and was inversely related to BMI (R2 = 0.140, p = 0.027). RNA sequencing revealed 331 and 280 genes that were differentially expressed after exercise in NO and O, respectively. Gene set enrichment analysis showed O had six blunted pathways related to metabolism, cell to cell communication, and protein turnover after exercise. The circulating amine response further highlighted dysregulations related to protein synthesis and metabolism in adults with obesity at the basal state and in response to the exercise bout. Collectively, these data highlight several unique pathways in individuals with obesity that resulted in a modestly blunted exercise response.
... After 6 weeks of heavy RT, muscle strength increases by 15% [66]. RT enhances the muscle protein synthesis ratio in humans by 50% at 4 hours after heavy resistance training [67]. ...
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PURPOSE: Minor skeletal muscle injuries can be repaired, but more extensive volumetric muscle loss (VML) leads to a permanent functional disability with ambiguous therapeutic outcomes, and reconstructive surgical procedures are constrained by donor tissue scarcity. This review assessed the considerable attention paid to biomaterials in healing damaged skeletal muscle.METHODS: A comprehensive search in PubMed, Web of Science, Google Scholar, and Wiley Online Library was conducted to obtain previous studies exploring the state of biocompatible tissue scaffolds for VML recovery.RESULTS: By regenerating the function of damaged skeletal muscle, tissue-engineered skeletal muscle construction could revolutionize the treatment of VML. However, transporting cells into the wounded muscle location presents a significant challenge because it may result in unfavorable immunological reactions. The development and validation of several biomaterials with varying physical and chemical natures to treat various muscle injuries have recently been undertaken to overcome this problem. This review discusses the relative benefits of satellite cells (SC), the most prevalent skeletal muscle stem cells employed to seed scaffolds.CONCLUSIONS: Biomaterials can be used with skeletal muscle stem cells and growth factors to repair VML because of their customizable and desirable physicochemical qualities. Owing to the capacity of SCs for self-renewal and their undifferentiated state, these cells are excellent candidates for cell therapy. A large gap exists between understanding SC behavior and how it can be used to repair and regenerate human skeletal muscle tissue. Thus, this review sought to portray the current knowledge on the lifespan of SCs and their involvement in exercise-induced muscle regeneration and hypertrophy.
Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill-trained. Much of the pre-clinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and post-exercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest additional mechanisms that feed into or are independent of these processes are also involved. This review will first provide a historical account as to how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms will be proposed.
The aim of this narrative review is to discuss the evidence on exercise for fall, fracture and sarcopenia prevention, including evidence that aligns with the specificity and progressive overload principles used in exercise physiology, implementation strategies and future research priorities. We also provide a brief discussion of the influence of protein intake and creatine supplementation as potential effect modifiers. We prioritized evidence from randomized controlled trials and systematic reviews. Resistance training can improve muscle mass, muscle strength and a variety of physical performance measures in older adults. Resistance training may also prevent bone loss or increase bone mass, although whether it needs to be done in combination with impact exercise to be effective is less clear, because many studies use combination interventions. Exercise programs prevent falls, and subgroup and network meta-analyses suggest an emphasis on balance and functional training, or specifically, anticipatory control, dynamic stability, functional stability limits, reactive control and flexibility, to maximize efficacy. Resistance training for major muscle groups at a 6–12 repetitions maximum intensity, and challenging balance exercises should be performed at least twice weekly. Choose resistance training exercises aligned with patient goals or movements done during daily activities (task specificity), alongside balance exercises tailored to ability and aspects of balance that need improvement. Progress the volume, level of difficulty or other aspects to see continuous improvement (progressive overload). A critical future priority will be to address implementation barriers and facilitators to enhance uptake and adherence.
Skeletal muscle is essential in locomotion and plays a role in whole-body metabolism, particularly during exercise. Skeletal muscle is the largest ‘reservoir’ of amino acids, which can be released for fuel and as a precursor for gluconeogenesis. During exercise, whole-body, and more specifically skeletal muscle, protein catabolism is increased, but protein synthesis is suppressed. Metabolism of skeletal muscle proteins can support energy demands during exercise, and persistent exercise (i.e. training) results in skeletal muscle protein remodelling. Exercise is generally classified as being either ‘strength’ or ‘aerobic/endurance’ in nature, and the type of exercise will reflect the phenotypic and metabolic adaptations of the muscle. In this chapter, we describe the impact of various exercise modes on protein metabolism during and following exercise.
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The purpose of this study was to investigate the magnitude and time course for changes in muscle protein synthesis (MPS) after a single bout of resistance exercise. Two groups of six male subjects performed heavy resistance exercise with the elbow flexors of one arm while the opposite arm served as a control. MPS from exercised (ex) and control (con) biceps brachii was assessed 4 (group A) and 24 h (group B) postexercise by the increment in L-[1-13C]leucine incorporation into muscle biopsy samples. In addition, RNA capacity and RNA activity were determined to assess whether transcriptional and/or translational processes affected MPS. MPS was significantly elevated in biceps of the ex compared with the con arms of both groups (group A, ex 0.1007 +/- 0.0330 vs. con 0.067 +/- 0.0204%/h; group B ex 0.0944 +/- 0.0363 vs. con 0.0452 +/- 0.0126%/h). RNA capacity was unchanged in the ex biceps of both groups relative to the con biceps, whereas RNA activity was significantly elevated in the ex biceps of both groups (group A, ex 0.19 +/- 0.10 vs. con 0.12 +/- 0.05 micrograms protein.h-1.microgram-1 total RNA; group B, ex 0.18 +/- 0.06 vs. con 0.08 +/- 0.02 micrograms protein.h-1.microgram-1 total RNA). The results indicate that a single bout of heavy resistance exercise can increase biceps MPS for up to 24 h postexercise. In addition, these increases appear to be due to changes in posttranscriptional events.
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The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague-Dawley rats after each was infused at a different rate with (1-13C)leucine for 6-8 h. Muscle leucine enrichment (at. % excess) measured by both methods differed by less than 4%, except at low (13C)leucine enrichments (less than 0.03 at. % excess). In addition, capillary GC/combustion IRMS was used to assess muscle (13C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13C2)leucine for 12-14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 +/- 0.011% h-1 (mean +/- SEM); range = 0.023-0.147% h-1) that agree with published values determined using the standard analytical approach. The measurement of (13C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS.
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The effects of resistance exercise upon leucine oxidation and whole body protein synthesis were studied using stable isotope methodology. L-[1-13C]leucine was used as a tracer to calculate leucine oxidation and whole body protein synthesis in six healthy, fed, male athletes in response to a 1 h bout of circuit-set resistance exercise. The measurements were performed prior to, during, and for 2 h after exercise, and corrections were made for background 13CO2/12CO2 breath enrichment and bicarbonate retention factor changes. Results demonstrated significant (P less than 0.01) increases in the background 13CO2/12CO2 breath enrichment at 1 and 2h after exercise and in the bicarbonate retention factor (P less than 0.01) during exercise. At 15 min after exercise, the bicarbonate retention factor was significantly (P less than 0.05) lower than at rest. There were no significant effects of exercise on leucine oxidation or flux, whole body protein synthesis, or the rate of appearance of endogenous leucine. We concluded that circuit-set resistance exercise did not affect the measured variables of leucine metabolism. In addition, large errors in calculating leucine oxidation and whole body protein synthesis during resistance exercise can occur if background 13CO2/12CO2 breath enrichment and bicarbonate retention factor changes are not accounted for.
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Muscle ultrastructure and contractile properties were examined before and after a single bout of resistance exercise (8 sets of 8 repetitions at 80% of 1 repetition maximum). Eight untrained males performed the concentric (Con) phase of arm-curl exercise with one arm and the eccentric (Ecc) phase with the other arm. Needle biopsies were obtained from biceps brachii before exercise (Base), immediately postexercise from each arm (post-Con and post-Ecc), and 48 h postexercise from each arm (48 h-Con and 48 h-Ecc). Electron microscopy was used to quantify the presence of disrupted fibers in each sample. Analysis of variance revealed a greater (P < or = 0.05) proportion of disrupted fibers in post-Con, post-Ecc, 48 h-Con, and 48 h-Ecc samples compared with Base. Significantly more fibers were disrupted in post-Ecc (82%) and 48 h-Ecc (80%) samples compared with post-Con (33%) and 48 h-Con (37%), respectively. Voluntary and evoked strength measurements recovered to Base values within 24 h in the Con arm but remained depressed (P < or = 0.05) for 72-96 h in the Ecc arm. These data indicate that both the raising and lowering phases of weightlifting produced myofibrillar disruption, with the greatest disruption occurring during the lowering phase.
In another study (J. Appl. Physiol. 69: 1709-1717, 1990) we reported that gastrocnemius (GAST) muscle enlargement failed to occur after 10 wk of 192 contractions performed every 3rd or 4th day. This result was surprising because increased protein synthesis rates were determined after an initial acute exercise bout with the same paradigms. In the same set of animals, tibialis anterior (TA) muscles were enlarged 16-30% compared with sedentary control muscles after the same chronic training regimen. This indicated that the regulation of protein expression may be different between the GAST and TA muscles. The present experiment attempted to define and explain these differences by comparing changes in various indexes of protein metabolism in TA with the same parameters determined in the accompanying study for the GAST. As in the GAST, results showed that TA protein synthesis rates are increased by acute exercise and principally regulated by translational and possibly posttranslational mechanisms. The differential response in muscle mass between the GAST and TA muscles after training may be due, in part, to greater relative resistances imposed on the TA than on the GAST that result in a more-prolonged effect on protein synthesis rates, with lower numbers of stimulated contractions required to stimulate increases in protein synthesis. Data also revealed that although as little as 1 min of total contractile duration (24 repetitions) increased TA protein synthesis rate by 30%, 8 min of total contractile duration (192 repetitions) further increased TA protein synthesis rates to only 45% above control.
Fractional mixed skeletal muscle protein synthesis (FMPS) was estimated in 10 postabsorptive healthy men by determining the increment in the abundance of [13C]-leucine in quadriceps muscle protein during an intravenous infusion of L-[1-13C]leucine. FMPS in our subjects was 0.046 +/- 0.003%/h. Whole-body muscle protein synthesis (MPS) was calculated based on the estimation of muscle mass from creatinine excretion and compared with whole-body protein synthesis (WBPS) calculated from the nonoxidative portion of leucine flux. A significant correlation (r2 = 0.73, P less than 0.05) was found between MPS (44.7 +/- 3.4 and WBPS (167.8 +/- 8.5 The contribution of MPS to WBPS was 27 +/- 1%, which is comparable to the reports in other species. Morphometric analyses of adjacent muscle samples in eight subjects demonstrated that the biopsy specimens consisted of 86.5 +/- 2% muscular as opposed to other tissues. Because fiber type composition varies between biopsies, we examined the relationship between proportions of each fiber type and FMPS. Variation in the composition of biopsies and in fiber-type proportion did not affect the estimation of muscle protein synthesis rate. We conclude that stable isotope techniques using serial needle biopsies permit the direct measurement of FMPS in humans and that this estimation is correlated with an indirect estimation of WBPS.
Seven healthy male subjects were studied under control conditions and following 5-6 months of heavy resistance training and 5-6 weeks of immobilization in elbow casts. Cross-sectional fibre areas and nuclei-to-fibre ratios were calculated from cryostat sections of needle biopsies taken from triceps brachii. Training resulted in a 98% increase in maximal elbow extension strength as measured by a Cybex dynamometer, while immobilization resulted in a 41% decrease in strength. Both fast twitch (FT) and slow twitch (ST) fibre areas increased significantly with training by 39% and 31%, respectively. Immobilization resulted in significant decreases in fibre area by 33% for FT and 25% for ST fibres. The observed nuclei-to-fibre ratio was 10% greater following the training programme. However, this change was non-significant. There was also a non-significant correlation between the magnitude of the changes in fibre size and the changes in maximal strength following either training or immobilization.