Role of Ingested Amino Acids and Protein in the Promotion of Resistance Exercise–Induced Muscle Protein Anabolism

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.

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Rapamycin‐insensitive mechanistic target of rapamycin regulates basal and resistance exercise‐induced muscle protein synthesis

The FASEB Journal ◽

10.1096/fj.201701422r ◽

2018 ◽

Vol 32 (11) ◽

pp. 5824-5834 ◽

Cited By ~ 20

Author(s):

Riki Ogasawara ◽

Takeshi Suginohara

Keyword(s):

Protein Synthesis ◽

Resistance Exercise ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Target Of Rapamycin ◽

Mechanistic Target Of Rapamycin ◽

Exercise Induced

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Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.00685.2018 ◽

2019 ◽

Vol 126 (1) ◽

pp. 30-43 ◽

Cited By ~ 45

Author(s):

Henning Wackerhage ◽

Brad J. Schoenfeld ◽

D. Lee Hamilton ◽

Maarit Lehti ◽

Juha J. Hulmi

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Muscle Damage ◽

Muscle Hypertrophy ◽

Muscle Protein ◽

Large Body ◽

Focal Adhesions ◽

Indirect Evidence ◽

Skeletal Muscle Hypertrophy ◽

Exercise Induced

One of the most striking adaptations to exercise is the skeletal muscle hypertrophy that occurs in response to resistance exercise. A large body of work shows that a mammalian target of rapamycin complex 1 (mTORC1)-mediated increase of muscle protein synthesis is the key, but not sole, mechanism by which resistance exercise causes muscle hypertrophy. While much of the hypertrophy signaling cascade has been identified, the initiating, resistance exercise-induced and hypertrophy-stimulating stimuli have remained elusive. For the purpose of this review, we define an initiating, resistance exercise-induced and hypertrophy-stimulating signal as “hypertrophy stimulus,” and the sensor of such a signal as “hypertrophy sensor.” In this review we discuss our current knowledge of specific mechanical stimuli, damage/injury-associated and metabolic stress-associated triggers, as potential hypertrophy stimuli. Mechanical signals are the prime hypertrophy stimuli candidates, and a filamin-C-BAG3-dependent regulation of mTORC1, Hippo, and autophagy signaling is a plausible albeit still incompletely characterized hypertrophy sensor. Other candidate mechanosensing mechanisms are nuclear deformation-initiated signaling or several mechanisms related to costameres, which are the functional equivalents of focal adhesions in other cells. While exercise-induced muscle damage is probably not essential for hypertrophy, it is still unclear whether and how such muscle damage could augment a hypertrophic response. Interventions that combine blood flow restriction and especially low load resistance exercise suggest that resistance exercise-regulated metabolites could be hypertrophy stimuli, but this is based on indirect evidence and metabolite candidates are poorly characterized.

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Intensive resistance exercise induces lymphocyte apoptosis via cortisol and glucocorticoid receptor-dependent pathways

Journal of Applied Physiology ◽

10.1152/japplphysiol.01295.2010 ◽

2011 ◽

Vol 110 (5) ◽

pp. 1226-1232 ◽

Cited By ~ 26

Author(s):

K. Krüger ◽

S. Agnischock ◽

A. Lechtermann ◽

S. Tiwari ◽

M. Mishra ◽

...

Keyword(s):

Resistance Exercise ◽

Glucocorticoid Receptors ◽

Resistance Test ◽

Apoptosis Induction ◽

Lymphocyte Apoptosis ◽

Reactive Protein ◽

Underlying Mechanisms ◽

Exercise Induced ◽

Moderate Resistance

Intensive endurance exercise is known to induce lymphocyte apoptosis, which might affect immune function. Less is known about the effects of resistance exercise on apoptosis and its underlying mechanisms. In this study, subjects performed an intensive resistance test (IRT) and a moderate resistance test, and lymphocyte apoptosis, apoptosis-related parameters, and underlying mechanisms were investigated. IRT induced a significant increase of lymphocyte apoptosis 3 h after exercise, which was accompanied by a significant decrease of mitochondrial membrane potential, a reduction of Bcl-2, and an upregulation of the CD95 receptor. Blood lactate, IL-6, C-reactive protein, and cortisol increased significantly 3 h after IRT. A significant correlation was observed between the increase of apoptosis and cortisol levels 3 h after IRT. Incubation of freshly isolated lymphocytes in IRT serum indicated an important role of serum correlates for apoptosis induction. Selective incubation of lymphocytes in concentrations of selected serum parameters corresponding to levels found post in IRT serum demonstrated a major role for cortisol in apoptosis induction. This result was confirmed by attenutation of apoptosis after addition of mifepristone before incubation in IRT serum. In summary, resistance exercise induced lymphocyte apoptosis in an intensity-dependent way. Furthermore, cortisol signaling via glucocorticoid receptors might be an important mechanism for lymphocyte apoptosis after resistance exercise.

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Increased net muscle protein balance in response to simultaneous and separate ingestion of carbohydrate and essential amino acids following resistance exercise

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2013-0264 ◽

2014 ◽

Vol 39 (3) ◽

pp. 329-339 ◽

Cited By ~ 6

Author(s):

Oliver C. Witard ◽

Tara L. Cocke ◽

Arny A. Ferrando ◽

Robert R. Wolfe ◽

Kevin D. Tipton

Keyword(s):

Amino Acids ◽

Resistance Exercise ◽

Acute Exercise ◽

Muscle Protein ◽

Exercise Bout ◽

Essential Amino Acids ◽

Delayed Response ◽

Protein Balance ◽

Post Exercise ◽

Exercise Muscle

Relative to essential amino acids (EAAs), carbohydrate (CHO) ingestion stimulates a delayed response of net muscle protein balance (NBAL). We investigated if staggered ingestion of CHO and EAA would superimpose the response of NBAL following resistance exercise, thus resulting in maximal anabolic stimulation. Eight recreationally trained subjects completed 2 trials: combined (COMB — drink 1, CHO+EAA; drink 2, placebo) and separated (SEP — drink 1, CHO; drink 2, EAA) post-exercise ingestion of CHO and EAA. Drink 1 was administered 1 h following an acute exercise bout and was followed 1 h later by drink 2. A primed, continuous infusion of l-[ring-13C6]-phenylalanine was combined with femoral arteriovenous sampling and muscle biopsies for the determination of muscle protein kinetics. Arterial amino acid concentrations increased following ingestion of EAA in both conditions. No difference between conditions was observed for phenylalanine delivery to the leg (COMB: 167 ± 23 μmol·min−1·(100 mL leg vol)−1 × 6 h; SEP: 167 ± 21 μmol·min−1·(100 mL leg vol)−1 × 6 h, P > 0.05). In the first hour following ingestion of the drink containing EAA, phenylalanine uptake was 50% greater for the SEP trial than the COMB trial. However, phenylalanine uptake was similar for COMB (110 ± 19 mg) and SEP (117 ± 24 mg) over the 6 h period. These data suggest that whereas separation of CHO and EAA ingestion following exercise may have a transient physiological impact on NBAL, this response is not reflected over a longer period. Thus, separation of CHO and EAA ingestion is unnecessary to optimize post-exercise muscle protein metabolism.

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Ursolic acid stimulates mTORC1 signaling after resistance exercise in rat skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00302.2013 ◽

2013 ◽

Vol 305 (6) ◽

pp. E760-E765 ◽

Cited By ~ 37

Author(s):

Riki Ogasawara ◽

Koji Sato ◽

Kazuhiko Higashida ◽

Koichi Nakazato ◽

Satoshi Fujita

Keyword(s):

Resistance Exercise ◽

Ursolic Acid ◽

Gastrocnemius Muscle ◽

Corn Oil ◽

Muscle Protein ◽

Akt Signaling ◽

Sprague Dawley ◽

Mtorc1 Signaling ◽

Exercise Induced ◽

Mtorc1 Activation

A recent study identified ursolic acid (UA) as a potent stimulator of muscle protein anabolism via PI3K/Akt signaling, thereby suggesting that UA can increase Akt-independent mTOR complex 1 (mTORC1) activation induced by resistance exercise via Akt signaling. The purpose of the present study was to investigate the effect of UA on resistance exercise-induced mTORC1 activation. The right gastrocnemius muscle of male Sprague-Dawley rats aged 11 wk was isometrically exercised via percutaneous electrical stimulation (stimulating ten 3-s contractions per set for 5 sets), while the left gastrocnemius muscle served as the control. UA or placebo (PLA; corn oil only) was injected intraperitoneally immediately after exercise. The rats were killed 1 or 6 h after the completion of exercise and the target tissues removed immediately. With placebo injection, the phosphorylation of p70S6K at Thr389 increased 1 h after resistance exercise but attenuated to the control levels 6 h after the exercise. On the other hand, the augmented phosphorylation of p70S6K was maintained even 6 h after exercise when UA was injected immediately after exercise. A similar trend of prolonged phosphorylation was observed in PRAS40 Thr246, whereas UA alone or resistance exercise alone did not alter its phosphorylation level at 6 h after intervention. These results indicate that UA is able to sustain resistance exercise-induced mTORC1 activity.

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Control of Muscle Protein Synthesis as a Result of Contractile Activity and Amino Acid Availability: Implications for Protein Requirements

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.11.s1.s170 ◽

2001 ◽

Vol 11 (s1) ◽

pp. S170-S176 ◽

Cited By ~ 12

Author(s):

Michael J. Rennie

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Muscle Protein ◽

Contractile Activity ◽

Muscle Protein Synthesis ◽

Protein Requirements ◽

Amino Acid Availability ◽

Separate Pathway

The major anabolic influences on muscle are feeding and contractile activity. As a result of feeding, anabolism occurs chiefly by increases in protein synthesis with minor changes in protein breakdown. Insulin has a permissive role in increasing synthesis, but the availability of amino acids is crucial for net anabolism. We have investigated the role of amino acids in stimulating muscle protein synthesis, the synergy between exercise and amino acid availability, and some of the signaling elements involved. The results suggest that muscle is acutely sensitive to amino acids, that exercise probably increases the anabolic effects of amino acids by a separate pathway, and that for this reason it is unlikely that accustomed physical exercise increases protein requirements.

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Improving muscle mass: response of muscle metabolism to exercise, nutrition and anabolic agents

Essays in Biochemistry ◽

10.1042/bse0440085 ◽

2008 ◽

Vol 44 ◽

pp. 85-98 ◽

Cited By ~ 38

Author(s):

Kevin D. Tipton ◽

Arny A. Ferrando

Keyword(s):

Amino Acids ◽

Resistance Exercise ◽

Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Creatine Supplementation ◽

Healthy Weight ◽

Anabolic Agents ◽

Increase Muscle Mass ◽

Positive Balance

Muscle mass is critical for athletic performance and, perhaps more importantly for most, health and survival. The metabolic basis for a change in muscle mass is an increase in net muscle protein balance (termed NBAL). NBAL is the difference between MPS (muscle protein synthesis) and MPB (muscle protein breakdown). Thus an increase in MPS and/or a decrease in MPB are necessary for NBAL to increase, leading to accretion of muscle proteins. In particular, accretion of myofibrillar proteins is necessary. NBAL responds to exercise, feeding and other factors. In healthy, weight-stable adults, muscle mass remains constant because periods of positive balance following feeding are countered by periods of negative balance during fasting. A combination of resistance exercise and nutrition is a potent anabolic stimulus through stimulation of MPS from amino acids and attenuation of MPB by carbohydrates. Increased muscle mass results from the accumulation of small amounts of protein in response to each bout of exercise combined with nutrient intake. The magnitude of the response may be influenced by factors other than just the amount of a nutrient ingested. Timing of ingestion, co-ingestion of nutrients and the type of protein may all influence protein accretion. Testosterone is a potent anabolic stimulus primarily through improvement in re-utilization of amino acids from MPB. There is a general lack of efficacy in studies assessing the potential for growth hormone, androstenedione and dehydroepiandrostenedione to increase muscle mass. Creatine supplementation is clearly an effective means to increase muscle mass, especially in combination with resistance exercise, however the mechanisms remain unclear. Results from acute metabolic studies provide useful information for estimation of the efficacy of anabolic agents.

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Exercise-Induced Muscle Damage and Hypertrophy: A Closer Look Reveals the Jury is Still Out

10.31236/osf.io/8a95z ◽

2018 ◽

Author(s):

Brad Jon Schoenfeld ◽

Bret Contreras

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Resistance Training ◽

Muscle Damage ◽

Muscle Hypertrophy ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Skeletal Muscle Hypertrophy ◽

Exercise Induced

This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potentiates increases in muscle hypertrophy. The intent of our letter is not to suggest that a causal role exists between hypertrophy and microinjury. Rather, we hope to provide balance to the evidence presented and offer the opinion that the jury is still very much out as to providing answers on the topic.

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More than just a garbage can: emerging roles of the lysosome as an anabolic organelle in skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00241.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. C561-C568

Author(s):

Sidney Abou Sawan ◽

Michael Mazzulla ◽

Daniel R. Moore ◽

Nathan Hodson

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Intracellular Signaling ◽

Muscle Protein ◽

Future Research ◽

Dietary Amino Acids ◽

Lysosome Biogenesis ◽

Transcription Factor Eb ◽

Mtorc1 Activation

Skeletal muscle is a highly plastic tissue capable of remodeling in response to a range of physiological stimuli, including nutrients and exercise. Historically, the lysosome has been considered an essentially catabolic organelle contributing to autophagy, phagocytosis, and exo-/endocytosis in skeletal muscle. However, recent evidence has emerged of several anabolic roles for the lysosome, including the requirement for autophagy in skeletal muscle mass maintenance, the discovery of the lysosome as an intracellular signaling hub for mechanistic target of rapamycin complex 1 (mTORC1) activation, and the importance of transcription factor EB/lysosomal biogenesis-related signaling in the regulation of mTORC1-mediated protein synthesis. We, therefore, propose that the lysosome is an understudied organelle with the potential to underpin the skeletal muscle adaptive response to anabolic stimuli. Within this review, we describe the molecular regulation of lysosome biogenesis and detail the emerging anabolic roles of the lysosome in skeletal muscle with particular emphasis on how these roles may mediate adaptations to chronic resistance exercise. Furthermore, given the well-established role of amino acids to support muscle protein remodeling, we describe how dietary proteins “labeled” with stable isotopes could provide a complementary research tool to better understand how lysosomal biogenesis, autophagy regulation, and/or mTORC1-lysosomal repositioning can mediate the intracellular usage of dietary amino acids in response to anabolic stimuli. Finally, we provide avenues for future research with the aim of elucidating how the regulation of this important organelle could mediate skeletal muscle anabolism.

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