Skeletal muscle adaptation is regulated by the balance between protein synthesis and protein breakdown rates. Muscle protein fractional synthesis rates (FSRs) can be determined by administration of stable isotope labeled amino acids and the subsequent measurement of their incorporation into muscle
Andrew M. Holwerda, Freek G. Bouwman, Miranda Nabben, Ping Wang, Janneau van Kranenburg, Annemie P. Gijsen, Jatin G. Burniston, Edwin C.M. Mariman and Luc J.C. van Loon
John C. Lawrence Jr.
Muscle mass is influenced by many factors including genetically programmed changes, hormonal state, level of activity, and disease processes. Ultimately, whether or not a muscle hypertrophies or atrophies is determined by a simple relationship between the rates of protein synthesis and degradation. When synthesis exceeds degradation, the muscle hypertrophies, and vice versa. In contrast to this simple relationship, the processes that control muscle protein synthesis and degradation are complex. Recently, significant progress has been made in understanding the biochemical mechanisms that control the rate of translation initiation, which is generally the limiting phase in protein synthesis.
Leonard S. Jefferson and Scot R. Kimball
Gain or loss of skeletal muscle mass is due largely to the establishment of an imbalance between rates of protein synthesis and degradation. A key determinant of the rate of protein synthesis is translation initiation, a process regulated in part through binding of initiator methionyl-tRNA (met-tRNAi) and messenger RNA (mRNA) to a 40S ribosomal subunit. Either the met-tRNAi or mRNA binding step can become limiting for protein synthesis. Furthermore, the mRNA binding step can modulate translation of specific mRNAs with or without changes in the overall rate of protein synthesis. This report highlights molecular mechanisms involved in mediating control of the mRNA binding step in translation initiation. Particular attention is given to the effect of exercise on this step and to how the branched-chain amino acid leucine stimulates muscle protein synthesis after exercise. Potential mechanisms for exercise induced increase in muscle mass are discussed.
James A. Betts, Milou Beelen, Keith A. Stokes, Wim H.M. Saris and Luc J.C. van Loon
Nocturnal endocrine responses to exercise performed in the evening and the potential role of nutrition are poorly understood. To gain novel insight, 10 healthy men ingested carbohydrate with (C+P) and without (C) protein in a randomized order and double-blind manner during 2 hr of interval cycling followed by resistancetype exercise and into early postexercise recovery. Blood samples were obtained hourly throughout 9 hr of postexercise overnight recovery for analysis of key hormones. Muscle samples were taken from the vastus lateralis before and after exercise and then again the next morning (7 a.m.) to calculate mixed-muscle protein fractional synthetic rate (FSR). Overnight plasma hormone concentrations were converted into overall responses (expressed as area under the concentration curve) and did not differ between treatments for either growth hormone (1,464 ± 257 vs. 1,432 ± 164 pg/ml · 540 min) or total testosterone (18.3 ± 1.2 vs. 17.9 ± 1.2 nmol/L · 540 min, C and C+P, respectively). In contrast, the overnight cortisol response was higher with C+P (102 ± 11 nmol/L · 540 min) than with C (81 ± 8 nmol/L · 540 min; p = .02). Mixed-muscle FSR did not differ between C and C+P during overnight recovery (0.062% ± 0.006% and 0.062% ± 0.009%/hr, respectively) and correlated significantly with the plasma total testosterone response (r = .7, p < .01). No correlations with FSR were apparent for the response of growth hormone (r = –.2, p = .4), cortisol (r = .1, p = .6), or the ratio of testosterone to cortisol (r = .2, p = .5). In conclusion, protein ingestion during and shortly after exercise does not modulate the endocrine response or muscle protein synthesis during overnight recovery.
Michael J. Rennie
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.
Resistance exercise can effectively result in an increase in muscle mass, or hypertrophy, which generally becomes apparent after several weeks of training. Muscle hypertrophy requires muscle protein synthesis to exceed protein breakdown during an extended time period. It has been firmly established that the interaction between exercise and nutrition (i.e., protein intake) is necessary to attain net protein accretion in skeletal muscle. The stimulation of protein synthesis is caused in part by stimulation of mRNA translation initiation. There is relatively little information on the response of intracellular signaling controlling mRNA translation to exercise and nutrition, especially in humans, but the available data in humans seem to suggest that a single bout of resistance exercise does not substantially enhance PI-3 kinase/mTOR signaling during the first 2 h after exercise. Moreover, it is demonstrated that the ingestion of protein or amino acids after exercise is crucial to further stimulate molecular signaling that controls translation initiation. The aim of this review is to provide an overview of the intracellular signaling related to translational control and to provide a summary of the current knowledge about the response of the signaling pathways controlling the anabolic response to exercise and nutrient intake in vivo in humans.
Louise M. Burke and Inigo Mujika
Postexercise recovery is an important topic among aquatic athletes and involves interest in the quality, quantity, and timing of intake of food and fluids after workouts or competitive events to optimize processes such as refueling, rehydration, repair, and adaptation. Recovery processes that help to minimize the risk of illness and injury are also important but are less well documented. Recovery between workouts or competitive events may have two separate goals: (a) restoration of body losses and changes caused by the first session to restore performance for the next and (b) maximization of the adaptive responses to the stress provided by the session to gradually make the body become better at the features of exercise that are important for performance. In some cases, effective recovery occurs only when nutrients are supplied, and an early supply of nutrients may also be valuable in situations in which the period immediately after exercise provides an enhanced stimulus for recovery. This review summarizes contemporary knowledge of nutritional strategies to promote glycogen resynthesis, restoration of fluid balance, and protein synthesis after different types of exercise stimuli. It notes that some scenarios benefit from a proactive approach to recovery eating, whereas others may not need such attention. In fact, in some situations it may actually be beneficial to withhold nutritional support immediately after exercise. Each athlete should use a cost–benefit analysis of the approaches to recovery after different types of workouts or competitive events and then periodize different recovery strategies into their training or competition programs.
Jill N. Schulte and Kevin E. Yarasheski
Advancing age is associated with a reduction in skeletal muscle protein, muscle strength, muscle quality, and chemical modifications that may impair protein function. Sarcopenia has been coupled with physical disability, frailty, and a loss of independent function (5, 19). Using stable isotope tracer methodologies and mass spectrometric detection, we observed: (a) 76–92-year-old physically frail and 62–74-year-old middle-age adults have lower mixed muscle protein synthetic rates than 20–32-year-old men and women; (b) 2 weeks and 3 months of weightlifting exercise increased the synthetic rate of myosin heavy chain (MHC) and mixed muscle proteins to a similar magnitude in frail, middle-age, and young women and men; (c) Serum myostatin-immunoreactive protein levels were elevated in physically frail women and were inversely correlated with lean mass. This suggests that the protein synthetic machinery adapts rapidly to increased contractile activity and that the adaptive response(s) are maintained even in frail elders.
Vandre C. Figueiredo, Michelle M. Farnfield, Megan L.R. Ross, Petra Gran, Shona L. Halson, Jonathan M. Peake, David Cameron-Smith and James F. Markworth
Resistance exercise is a potent stimulus for muscle protein turnover, enhancing rates of both protein synthesis and degradation ( Koopman et al., 2007 ; Wolfe, 2006 ). The beneficial action of nutrient provision is well established to amplify the anabolic response to resistance exercise
Stefan M. Pasiakos, Holly L. McClung, James P. McClung, Maria L. Urso, Matthew A. Pikosky, Gregory J. Cloutier, Roger A. Fielding and Andrew J. Young
This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 ± 1 yr, body mass 80 ± 2 kg, and VO2peak 45 ± 1 ml · kg−1 · min−1) immediately (0 hr) and 3 hr after a 60-min bout of cycle exercise (60% ± 5% VO2peak). Corresponding muscle biopsies were also obtained under resting conditions. The phosphorylation status of insulin/IGF-PI3K molecular-signaling proteins, ubiquitin-proteasome-related gene expression, FOXO transcription factors, and myogenic regulatory factors in muscle samples was analyzed using multiplex analysis, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). A condition–time interaction was observed for Akt phosphorylation (p < .05) with multiplexing. Regardless of endurance exercise, Akt phosphorylation decreased and ERK phosphorylation increased at 3 hr compared with 0 hr (p < .05). Levels of p70S6K phosphorylation were 110% greater (p < .05) at 3 hr than at 0 hr using Western blots. MuRF mRNA expression postexercise increased; levels were 4.7- and 5.7-fold greater (p < .05) at 0 hr and 3 hr, respectively, than at rest with qRT-PCR. Atrogin mRNA expression was up-regulated 3.2-fold 3 hr postexercise compared with rest. These findings demonstrate modest changes in the molecular responses to moderate endurance exercise in the absence of nutrition. This study provides the groundwork for future investigations designed to optimize the metabolic conditions necessary to positively influence the cellular mechanisms specific to skeletal-muscle protein turnover during recovery from endurance exercise.