Activation of mTOR signalling in young and old human skeletal muscle in response to combined resistance exercise and whey protein ingestion

2012 ◽  
Vol 37 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Michelle M. Farnfield ◽  
Leigh Breen ◽  
Kate A. Carey ◽  
Andrew Garnham ◽  
David Cameron-Smith

Purpose: To investigate the impact of whey protein ingestion and resistance exercise training on the phosphorylation of mRNA translational signalling proteins in the skeletal muscle of young and old men. Methods: Sixteen healthy young (aged 18–25 years) and 15 healthy older men (aged 60–75 years) completed 12 weeks of resistance exercise and were randomly assigned to consume a whey protein (WPI) or placebo drink after each session. Muscle biopsies were collected before and 2 h after an acute exercise bout at the beginning and the end of training. Results: All subjects significantly increased strength after following strength training. Phosphorylation of mTOR was significantly greater in the WPI groups compared with placebo for both younger and older subjects. Phosphorylation of p70S6K, eIF4G, and 4EBP1 was greater for older subjects consuming WPI. Phosphorylation of rpS6, eIF4G, and 4EBP1 tended to increase in the younger subjects that had consumed WPI. Post-training, younger subjects demonstrated a similar pattern of mTOR phosphorylation as seen pre-training. In contrast, the initial heightened phosphorylation of mTOR, p70S6K, rpS6, and eIF4G in older muscle to combined resistance exercise and WPI ingestion became less pronounced after repeated training sessions. Conclusions: In the untrained state, resistance exercise coupled with WPI increases the phosphorylation of proteins involved in mRNA translation compared with exercise alone. Post-training, WPI- and exercise-induced protein phosphorylation was reduced in older men, but not in younger men. Thus, strategies to induce hypertrophy should utilize protein and resistance training concurrently. Further investigations should delineate interventions that will maintain sensitivity to anabolic stimuli in older populations.

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 641 ◽  
Author(s):  
Ana P. Pinto ◽  
Tales S. Vieira ◽  
Bruno B. Marafon ◽  
Gabriela Batitucci ◽  
Elisa M. B. Cabrera ◽  
...  

The present study verified the responses of proteins related to the autophagy pathway after 10 h of fast with resistance exercise and protein ingestion in skeletal muscle and liver samples. The rats were distributed into five experimental groups: control (CT; sedentary and without gavage after fast), exercise immediately (EXE-imm; after fast, rats were submitted to the resistance protocol and received water by gavage immediately after exercise), exercise after 1 h (EXE-1h; after fast, rats were submitted to the resistance protocol and received water by gavage 1 h after exercise), exercise and supplementation immediately after exercise (EXE/Suppl-imm; after fast, rats were submitted to the resistance protocol and received a mix of casein: whey protein 1:1 (w/w) by gavage immediately after exercise), exercise and supplementation 1 h after exercise (EXE/Suppl-1h; after fast, rats were submitted to the resistance protocol and received a mix of casein: whey protein 1:1 (w/w) by gavage 1 h after exercise). In summary, the current findings show that the combination of fasting, acute resistance exercise, and protein blend ingestion (immediately or 1 h after the exercise stimulus) increased the serum levels of leucine, insulin, and glucose, as well as the autophagy protein contents in skeletal muscle, but decreased other proteins related to the autophagic pathway in the liver. These results deserve further mechanistic investigations since athletes are combining fasting with physical exercise to enhance health and performance outcomes.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 656-656
Author(s):  
Amadeo Salvador ◽  
Colleen McKenna ◽  
Andrew Askow ◽  
Hsin-Yu Fang ◽  
Sarah Burke ◽  
...  

Abstract Objectives Yes-Associated Protein (YAP) is implicated as a regulator of the post-exercise skeletal muscle response through mechanical transduction. We recently observed that resistance exercise (RE) increased both total (t) and phosphorylated (p) muscle YAP content, which correlated with extracellular signal-regulated kinase 1/2 (Erk1/2). Other anabolic signaling pathways (i.e., mTORC1) are known to be potentiated by the combined stimuli of RE and protein ingestion during post-exercise recovery. However, the impact of protein ingestion on t- and p-muscle YAP content during recovery from RE is unknown. Therefore, we aimed to determine the nutrient sensitivity of YAP in both an acute and chronic exercise setting in aging skeletal muscle. Methods Acute study: 13 untrained older women (59.8 ± 0.5 y) were randomized to perform an acute bout of unilateral RE (3 sets × 12 repetitions at 65% of one repetition maximum) followed by the ingestion of whey protein (0.3 g/kg lean body mass) or water. Muscle biopsies of both the rested and exercised legs were collected before and during the postprandial period. Chronic study: 20 untrained middle-aged men and women (47.5 ± 0.3 y) performed 3 weeks of whole body RE (3 d/wk) with moderate or high protein intake set at 1.2 g/kg/d or 1.6 g/kg/d, respectively. Muscle biopsies were taken weekly in the rested state. Total and phosphorylated YAPSer127 and Erk1/2Thr202/Tyr204 were examined by western blotting. Results Acute study: Protein ingestion decreased t- and p-YAP compared to the water condition in the non-exercised leg (main effect: P < 0.04). There was no change in t- or p-YAP, regardless of condition, in the exercised-leg throughout recovery (P = 0.88). There was no change in p/t ratio of Erk1/2 in the exercised or non-exercised leg.  Chronic study: There was no change in either p- or t-YAP in moderate and high protein conditions throughout training (both, P > 0.05). There was a decrease in t-Erk1/2 irrespective of condition (P = 0.04). There was no change in p/t ratio of Erk1/2 throughout training. There was a significant correlation between t-Erk1/2 and t-YAP (r = 0.741 and P < 0.001). Conclusions Protein ingestion mediated an acute down-regulation of YAP in the postprandial-state. However, resistance training did not modulate YAP content in aged skeletal muscle tissue. Funding Sources Funded by Beef Checkoff. AFS is supported by CAPES-Brazil.


2009 ◽  
Vol 297 (5) ◽  
pp. R1441-R1451 ◽  
Author(s):  
Vernon G. Coffey ◽  
Bozena Jemiolo ◽  
Johann Edge ◽  
Andrew P. Garnham ◽  
Scott W. Trappe ◽  
...  

We examined acute molecular responses in skeletal muscle to repeated sprint and resistance exercise bouts. Six men [age, 24.7 ± 6.3 yr; body mass, 81.6 ± 7.3 kg; peak oxygen uptake, 47 ± 9.9 ml·kg−1·min−1; one repetition maximum (1-RM) leg extension 92.2 ± 12.5 kg; means ± SD] were randomly assigned to trials consisting of either resistance exercise (8 × 5 leg extension, 80% 1-RM) followed by repeated sprints (10 × 6 s, 0.75 N·m torque·kg−1) or vice-versa. Muscle biopsies from vastus lateralis were obtained at rest, 15 min after each exercise bout, and following 3-h recovery to determine early signaling and mRNA responses. There was divergent exercise order-dependent phosphorylation of p70 S6K (S6K). Specifically, initial resistance exercise increased S6K phosphorylation (∼75% P < 0.05), but there was no effect when resistance exercise was undertaken after sprints. Exercise decreased IGF-I mRNA following 3-h recovery (∼50%, P = 0.06) independent of order, while muscle RING finger mRNA was elevated with a moderate exercise order effect ( P < 0.01). When resistance exercise was followed by repeated sprints PGC-1α mRNA was increased (REX1-SPR2; P = 0.02) with a modest distinction between exercise orders. Repeated sprints may promote acute interference on resistance exercise responses by attenuating translation initiation signaling and exacerbating ubiquitin ligase expression. Indeed, repeated sprints appear to generate the overriding acute exercise-induced response when undertaking concurrent repeated sprint and resistance exercise. Accordingly, we suggest that sprint-activities are isolated from resistance training and that adequate recovery time is considered within periodized training plans that incorporate these divergent exercise modes.


2011 ◽  
Vol 301 (3) ◽  
pp. E456-E466 ◽  
Author(s):  
Boubacar Benziane ◽  
Ulrika Widegren ◽  
Sergej Pirkmajer ◽  
Jan Henriksson ◽  
Nigel K. Stepto ◽  
...  

Phospholemman (PLM, FXYD1) is a partner protein and regulator of the Na+-K+-ATPase (Na+-K+ pump). We explored the impact of acute and short-term training exercise on PLM physiology in human skeletal muscle. A group of moderately trained males ( n = 8) performed a 1-h acute bout of exercise by utilizing a one-legged cycling protocol. Muscle biopsies were taken from vastus lateralis at 0 and 63 min (non-exercised leg) and 30 and 60 min (exercised leg). In a group of sedentary males ( n = 9), we determined the effect of a 10-day intense aerobic cycle training on Na+-K+-ATPase subunit expression, PLM phosphorylation, and total PLM expression as well as PLM phosphorylation in response to acute exercise (1 h at ∼72% V̇o2peak). Biopsies were taken at rest, immediately following, and 3 h after an acute exercise bout before and at the conclusion of the 10-day training study. PLM phosphorylation was increased both at Ser63 and Ser68 immediately after acute exercise (75%, P < 0.05, and 30%, P < 0.05, respectively). Short-term training had no adaptive effect on PLM phosphorylation at Ser63 and Ser68, nor was the total amount of PLM altered posttraining. The protein expressions of α1-, α2-,and β1-subunits of Na+-K+-ATPase were increased after training (113%, P < 0.05, 49%, P < 0.05, and 27%, P < 0.05, respectively). Whereas an acute bout of exercise increased the phosphorylation of PKCα/βII on Thr638/641 pre- and posttraining, phosphorylation of PKCζ/λ on Thr403/410 was increased in response to acute exercise only after the 10-day training. In conclusion, we show that only acute exercise, and not short-term training, increases phosphorylation of PLM on Ser63 and Ser68, and data from one-legged cycling indicate that this effect of exercise on PLM phosphorylation is not due to systemic factors. Our results provide evidence that phosphorylation of PLM may play a role in the acute regulation of the Na+-K+-ATPase response to exercise.


2013 ◽  
Vol 114 (1) ◽  
pp. 66-72 ◽  
Author(s):  
Peter Marklund ◽  
C. Mikael Mattsson ◽  
Britta Wåhlin-Larsson ◽  
Elodie Ponsot ◽  
Björn Lindvall ◽  
...  

The impact of a 24-h ultraendurance exercise bout on systemic and local muscle inflammatory reactions was investigated in nine experienced athletes. Blood and muscle biopsies were collected before (Pre), immediately after the exercise bout (Post), and after 28 h of recovery (Post28). Circulating blood levels of leukocytes, creatine kinase (CK), C-reactive protein (CRP), and selected inflammatory cytokines were assessed together with the evaluation of the occurrence of inflammatory cells (CD3+, CD8+, CD68+) and the expression of major histocompatibility complex class I (MHC class I) in skeletal muscle. An extensive inflammatory cell infiltration occurred in all athletes, and the number of CD3+, CD8+, and CD68+ cells were two- to threefold higher at Post28 compared with Pre ( P < 0.05). The inflammatory cell infiltration was associated with a significant increase in the expression of MHC class I in muscle fibers. There was a significant increase in blood leukocyte count, IL-6, IL-8, CRP, and CK at Post. At Post28, total leukocytes, IL-6, and CK had declined, whereas IL-8 and CRP continued to increase. Increases in IL-1β and TNF-α were not significant. There were no significant associations between the magnitude of the systemic and local muscle inflammatory reactions. Signs of muscle degenerative and regenerative events were observed in all athletes with various degrees of severity and were not affected by the 24-h ultraendurance exercise bout. In conclusion, a low-intensity but very prolonged single-endurance exercise bout can generate a strong inflammatory cell infiltration in skeletal muscle of well-trained experienced ultraendurance athletes, and the amplitude of the local reaction is not proportional to the systemic inflammatory response.


1997 ◽  
Vol 82 (5) ◽  
pp. 1411-1415 ◽  
Author(s):  
David N. Proctor ◽  
Michael J. Joyner

Proctor, David N., and Michael J. Joyner. Skeletal muscle mass and the reduction ofV˙o 2 max in trained older subjects. J. Appl. Physiol.82(5): 1411–1415, 1997.—The role of skeletal muscle mass in the age-associated decline in maximal O2 uptake (V˙o 2 max) is poorly defined because of confounding changes in muscle oxidative capacity and in body fat and the difficulty of quantifying active muscle mass during exercise. We attempted to clarify these issues by examining the relationship between several indexes of muscle mass, as estimated by using dual-energy X-ray absorptiometry and treadmillV˙o 2 max in 32 chronically endurance-trained subjects from four groups ( n = 8/group): young men (20–30 yr), older men (56–72 yr), young women (19–31 yr), and older women (51–72 yr).V˙o 2 max per kilogram body mass was 26 and 22% lower in the older men (45.9 vs. 62.0 ml ⋅ kg−1 ⋅ min−1) and older women (40.0 vs. 51.5 ml ⋅ kg−1 ⋅ min−1). These age differences were reduced to 14 and 13%, respectively, whenV˙o 2 max was expressed per kilogram of appendicular muscle. When appropriately adjusted for age and gender differences in appendicular muscle mass by analysis of covariance, whole bodyV˙o 2 max was 0.50 ± 0.09 l/min less ( P < 0.001) in the older subjects. This effect was similar in both genders. These findings suggest that the reducedV˙o 2 max seen in highly trained older men and women relative to their younger counterparts is due, in part, to a reduced aerobic capacity per kilogram of active muscle independent of age-associated changes in body composition, i.e., replacement of muscle tissue by fat. Because skeletal muscle adaptations to endurance training can be well maintained in older subjects, the reduced aerobic capacity per kilogram of muscle likely results from age-associated reductions in maximal O2 delivery (cardiac output and/or muscle blood flow).


1999 ◽  
Vol 276 (1) ◽  
pp. E118-E124 ◽  
Author(s):  
S. M. Phillips ◽  
K. D. Tipton ◽  
A. A. Ferrando ◽  
R. R. Wolfe

We examined the effect of resistance training on the response of mixed muscle protein fractional synthesis (FSR) and breakdown rates (FBR) by use of primed constant infusions of [2H5]phenylalanine and [15N]phenylalanine, respectively, to an isolated bout of pleiometric resistance exercise. Trained subjects, who were performing regular resistance exercise (trained, T; n = 6), were compared with sedentary, untrained controls (untrained, UT; n = 6). The exercise test consisted of 10 sets (8 repetitions per set) of single-leg knee flexion (i.e., pleiometric muscle contraction during lowering) at 120% of the subjects’ predetermined single-leg 1 repetition maximum. Subjects exercised one leg while their contralateral leg acted as a nonexercised (resting) control. Exercise resulted in an increase, above resting, in mixed muscle FSR in both groups (UT: rest, 0.036 ± 0.002; exercise, 0.0802 ± 0.01; T: rest, 0.045 ± 0.004; exercise, 0.067 ± 0.01; all values in %/h; P< 0.01). In addition, exercise resulted in an increase in mixed muscle FBR of 37 ± 5% (rest, 0.076 ± 0.005; exercise, 0.105 ± 0.01; all values in %/h; P < 0.01) in the UT group but did not significantly affect FBR in the T group. The resulting muscle net balance (FSR − FBR) was negative throughout the protocol ( P < 0.05) but was increased in the exercised leg in both groups ( P < 0.05). We conclude that pleiometric muscle contractions induce an increase in mixed muscle protein synthetic rate within 4 h of completion of an exercise bout but that resistance training attenuates this increase. A single bout of pleiometric muscle contractions also increased the FBR of mixed muscle protein in UT but not in T subjects.


Author(s):  
Geoffrey Warnier ◽  
Estelle De Groote ◽  
Florian A. Britto ◽  
Ophélie Delcorte ◽  
Joshua P. Nederveen ◽  
...  

Purpose: To investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Methods: Seventeen healthy (BMI: 23.5±0.5kg·m-2) and fifteen prediabetic (BMI: 27.3±1.2kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia (FiO2 14.0%). Venous blood samples were taken before (T0), during (T30) and after (T60) exercise and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. Results: In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81 and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX and CD9 were upregulated in skeletal muscle after exercise in normoxia; whereas, CD9 and CD81 were downregulated in hypoxia. Conclusions: ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.


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