scholarly journals Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B

2003 ◽  
Vol 284 (3) ◽  
pp. E488-E498 ◽  
Author(s):  
Hisamine Kobayashi ◽  
Elisabet Børsheim ◽  
Tracy G. Anthony ◽  
Daniel L. Traber ◽  
John Badalamenti ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Amino Acid Replacement ◽  
Plasma Amino Acid ◽  
Initiation Factor ◽  
Nucleotide Exchange ◽  
Amino Acid Availability ◽  
Amino Acid Concentrations

We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using [2H5]phenylalanine and [1-13C]leucine and analysis of femoral arterial and venous samples and tissue biopsies. Net amino acid release by muscle was accelerated during dialysis. Phenylalanine utilization for muscle protein synthesis was reduced from the basal value of 45 ± 8 to 25 ± 6 nmol · min−1 · 100 ml leg−1 between 30 and 60 min after start of dialysis and was stimulated when amino acids were replaced while dialysis continued. Muscle protein breakdown was unchanged. The signal for changes in synthesis appeared to be changes in plasma amino acid concentrations, as intramuscular concentrations remained constant throughout. The changes in muscle protein synthesis were accompanied by a reduction or stimulation, respectively, in the guanine nucleotide exchange activity of eukaryotic initiation factor (eIF)2B following hypoaminoacidemia vs. amino acid replacement. We conclude that a reduction in plasma amino acid concentrations below the normal basal value signals an inhibition of muscle protein synthesis and that corresponding changes in eIF2B activity suggest a possible role in mediating the response.

Whey and casein labeled with l-[1-13C]leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion

2011 ◽  
Vol 300 (1) ◽  
pp. E231-E242 ◽  
Author(s):  
Søren Reitelseder ◽  
Jakob Agergaard ◽  
Simon Doessing ◽  
Ida C. Helmark ◽  
Peter Lund ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Myofibrillar Protein ◽  
Western Blots ◽  
Amino Acid Availability ◽  
Amino Acid Concentrations ◽  
Myofibrillar Protein Synthesis

Muscle protein turnover following resistance exercise and amino acid availability are relatively well described. By contrast, the beneficial effects of different sources of intact proteins in relation to exercise need further investigation. Our objective was to compare muscle anabolic responses to a single bolus intake of whey or casein after performance of heavy resistance exercise. Young male individuals were randomly assigned to participate in two protein trials ( n = 9) or one control trial ( n = 8). Infusion of l-[1-13C]leucine was carried out, and either whey, casein (0.3 g/kg lean body mass), or a noncaloric control drink was ingested immediately after exercise. l-[1-13C]leucine-labeled whey and casein were used while muscle protein synthesis (MPS) was assessed. Blood and muscle tissue samples were collected to measure systemic hormone and amino acid concentrations, tracer enrichments, and myofibrillar protein synthesis. Western blots were used to investigate the Akt signaling pathway. Plasma insulin and branched-chain amino acid concentrations increased to a greater extent after ingestion of whey compared with casein. Myofibrillar protein synthesis was equally increased 1–6 h postexercise after whey and casein intake, both of which were higher compared with control ( P < 0.05). Phosphorylation of Akt and p70S6K was increased after exercise and protein intake ( P < 0.05), but no differences were observed between the types of protein except for total 4E-BP1, which was higher after whey intake than after casein intake ( P < 0.05). In conclusion, whey and casein intake immediately after resistance exercise results in an overall equal MPS response despite temporal differences in insulin and amino acid concentrations and 4E-BP1.

scholarly journals Ingestion of an ample amount of meat substitute based upon a lysine-enriched, plant-based protein blend stimulates postprandial muscle protein synthesis to a similar extent as an isonitrogenous amount of chicken in healthy, young men

2021 ◽  
pp. 1-28
Author(s):  
Imre W.K. Kouw ◽  
Philippe J.M. Pinckaers ◽  
Cindy Le Bourgot ◽  
Janneau M.X. van Kranenburg ◽  
Antoine H. Zorenc ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
G Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Product ◽  
Plasma Amino Acid ◽  
Similar Extent ◽  
Protein Sources ◽  
Amino Acid Concentrations

Abstract Plant-based proteins are considered to be less effective in their capacity to stimulate muscle protein synthesis when compared with animal-based protein sources, likely due to differences in amino acid contents. We compared the postprandial muscle protein synthetic response following the ingestion of a lysine-enriched plant-based protein product with an isonitrogenous amount of chicken. Twenty-four men (age: 24±5 y; BMI: 22.9±2.6 kg·m−2) participated in this parallel, double-blind, randomised controlled trial and consumed 40 g protein as a lysine-enriched wheat and chickpea protein product (Plant, n=12) or chicken breast fillet (Chicken, n=12). Primed, continuous intravenous L-[ring-13C6]-phenylalanine infusions were applied while repeated blood and muscle samples were collected over a 5h postprandial period to assess plasma amino acid responses, muscle protein synthesis rates, and muscle anabolic signalling responses. Postprandial plasma leucine and essential amino acid concentrations were higher following Chicken (P<0.001), while plasma lysine concentrations were higher throughout in Plant (P<0.001). Total plasma amino acid concentrations did not differ between interventions (P=0.181). Ingestion of both Plant and Chicken increased muscle protein synthesis rates from post-absorptive: 0.031±0.011 and 0.031±0.013 to postprandial: 0.046±0.010 and 0.055±0.015%∙h−1, respectively (P-time<0.001), with no differences between Plant and Chicken (P-interaction=0.068). Ingestion of 40 g protein in the form of a lysine-enriched plant-based protein product increases muscle protein synthesis rates to a similar extent as an isonitrogenous amount of chicken in healthy, young men. Plant-based protein products sold as meat replacers may be as effective as animal-based protein sources to stimulate postprandial muscle protein synthesis rates in healthy, young individuals.

scholarly journals Stimulation of Muscle Protein Synthesis by Prolonged Parenteral Infusion of Leucine Is Dependent on Amino Acid Availability in Neonatal Pigs

2009 ◽  
Vol 140 (2) ◽  
pp. 264-270 ◽  
Author(s):  
Fiona A. Wilson ◽  
Agus Suryawan ◽  
Maria C. Gazzaneo ◽  
Renán A. Orellana ◽  
Hanh V. Nguyen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Neonatal Pigs ◽  
Amino Acid Availability ◽  
Stimulation Of

Dexamethasone inhibits the stimulation of muscle protein synthesis and PHAS-I and p70 S6-kinase phosphorylation

2001 ◽  
Vol 280 (4) ◽  
pp. E570-E575 ◽  
Author(s):  
Wen Long ◽  
Liping Wei ◽  
Eugene J. Barrett
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Initiation Factor ◽  
Glucose Disposal ◽  
Acid Mixture ◽  
S6 Kinase ◽  
P70 S6 Kinase ◽  
Amino Acid Infusion

Glucocorticoids inhibit protein synthesis in muscle. In contrast, insulin and amino acids exert anabolic actions that arise in part from their ability to phosphorylate ribosomal p70 S6-kinase (p70S6k) and eukaryotic initiation factor (eIF)4E binding protein (BP)1 (PHAS-I), proteins that regulate translation initiation. Whether glucocorticoids interfere with this action was examined by giving rats either dexamethasone (DEX, 300 μg · kg−1 · day−1, n = 10) or saline ( n = 10) for 5 days. We then measured the phosphorylation of PHAS-I and p70S6kin rectus muscle biopsies taken before and at the end of a 180-min infusion of either insulin (10 mU · min−1 · kg−1 euglycemic insulin clamp, n = 5 for both DEX- and saline-treated groups) or a balanced amino acid mixture ( n = 5 for each group also). Protein synthesis was also measured during the infusion period. The results were that DEX-treated rats had higher fasting insulin, slower glucose disposal, less lean body mass, and decreased protein synthetic rates during insulin or amino acid infusion ( P < 0.05 each). DEX did not affect basal PHAS-I or p70S6k phosphorylation but blocked insulin-stimulated phosphorylation of PHAS-I- and amino acid-stimulated phosphorylation of both PHAS-I and p70S6k ( P < 0.01, for each). DEX also increased muscle PHAS-I concentration. These effects can, in part, explain glucocorticoid-induced muscle wasting.

Human muscle protein synthesis and breakdown during and after exercise

2009 ◽  
Vol 106 (6) ◽  
pp. 2026-2039 ◽  
Author(s):  
Vinod Kumar ◽  
Philip Atherton ◽  
Kenneth Smith ◽  
Michael J. Rennie
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Protein Turnover ◽  
Acute Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mitochondrial Protein ◽  
Human Muscle ◽  
Muscle Protein Turnover ◽  
Amino Acid Availability

Skeletal muscle demonstrates extraordinary mutability in its responses to exercise of different modes, intensity, and duration, which must involve alterations of muscle protein turnover, both acutely and chronically. Here, we bring together information on the alterations in the rates of synthesis and degradation of human muscle protein by different types of exercise and the influences of nutrition, age, and sexual dimorphism. Where possible, we summarize the likely changes in activity of signaling proteins associated with control of protein turnover. Exercise of both the resistance and nonresistance types appears to depress muscle protein synthesis (MPS), whereas muscle protein breakdown (MPB) probably remains unchanged during exercise. However, both MPS and MPB are elevated after exercise in the fasted state, when net muscle protein balance remains negative. Positive net balance is achieved only when amino acid availability is increased, thereby raising MPS markedly. However, postexercise-increased amino acid availability is less important for inhibiting MPB than insulin, the secretion of which is stimulated most by glucose availability, without itself stimulating MPS. Exercise training appears to increase basal muscle protein turnover, with differential responses of the myofibrillar and mitochondrial protein fractions to acute exercise in the trained state. Aging reduces the responses of myofibrillar protein and anabolic signaling to resistance exercise. There appear to be few, if any, differences in the response of young women and young men to acute exercise, although there are indications that, in older women, the responses may be blunted more than in older men.

Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation

2005 ◽  
Vol 288 (5) ◽  
pp. E914-E921 ◽  
Author(s):  
Jeffery Escobar ◽  
Jason W. Frank ◽  
Agus Suryawan ◽  
Hanh V. Nguyen ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Neonatal Pigs ◽  
Plasma Leucine

Protein synthesis in skeletal muscle of adult rats increases in response to oral gavage of supraphysiological doses of leucine. However, the effect on protein synthesis of a physiological rise in plasma leucine has not been investigated in neonates, an anabolic population highly sensitive to amino acids and insulin. Therefore, in the current study, fasted pigs were infused intra-arterially with leucine (0, 200, or 400 μmol·kg−1·h−1), and protein synthesis was measured after 60 or 120 min. Protein synthesis was increased in muscle, but not in liver, at 60 min. At 120 min, however, protein synthesis returned to baseline levels in muscle but was reduced below baseline values in liver. The increase in protein synthesis in muscle was associated with increased plasma leucine of 1.5- to 3-fold and no change in plasma insulin. Leucine infusion for 120 min reduced plasma essential amino acid levels. Phosphorylation of eukaryotic initiation factor (eIF)-4E-binding protein-1 (4E-BP1), ribosomal protein (rp) S6 kinase, and rpS6 was increased, and the amount of eIF4E associated with its repressor 4E-BP1 was reduced after 60 and 120 min of leucine infusion. No change in these biomarkers of mRNA translation was observed in liver. Thus a physiological increase in plasma leucine stimulates protein synthesis in skeletal muscle of neonatal pigs in association with increased eIF4E availability for eIF4F assembly. This response appears to be insulin independent, substrate dependent, and tissue specific. The results suggest that the branched-chain amino acid leucine can act as a nutrient signal to stimulate protein synthesis in skeletal muscle of neonates.

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

2001 ◽  
Vol 11 (s1) ◽  
pp. S170-S176 ◽  
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.

scholarly journals Ectopic expression of eIF2Bε in rat skeletal muscle rescues the sepsis-induced reduction in guanine nucleotide exchange activity and protein synthesis

2010 ◽  
Vol 299 (2) ◽  
pp. E241-E248 ◽  
Author(s):  
Alexander P. Tuckow ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
Leonard S. Jefferson
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Ectopic Expression ◽  
Initiation Factor ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Rat Skeletal Muscle ◽  
Guanine Nucleotide Exchange

Eukaryotic initiation factor 2B (eIF2B) is a guanine nucleotide exchange factor (GEF) whose activity is both tightly regulated and rate-controlling with regard to global rates of protein synthesis. Skeletal muscle eIF2B activity and expression of its catalytic ε-subunit (eIF2Bε) have been implicated as potential contributors to the altered rates of protein synthesis in a number of physiological conditions and experimental models. The objective of this study was to directly examine the effects of exogenously expressed eIF2Bε in vivo on GEF activity and protein synthetic rates in rat skeletal muscle. A plasmid encoding FLAG-eIF2Bε was transfected into the tibialis anterior (TA) of one leg, while the contralateral TA received a control plasmid. Ectopic expression of eIF2Bε resulted in increased GEF activity in TA homogenates of healthy rats, demonstrating that the expressed protein was catalytically active. In an effort to restore a deficit in eIF2B activity, we utilized an established model of chronic sepsis in which skeletal muscle eIF2B activity is known to be impaired. Ectopic expression of eIF2Bε in the TA rescued the sepsis-induced deficit in GEF activity and muscle protein synthesis. The results demonstrate that modulation of eIF2Bε expression may be sufficient to correct deficits in skeletal muscle protein synthesis associated with sepsis and other muscle-wasting conditions.

scholarly journals Effects of Salmon Ingestion on Post-Exercise Muscle Protein Synthesis: Exploration of Whole Protein Foods Versus Isolated Nutrients

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 650-650
Author(s):  
Kevin Paulussen ◽  
Amadeo Salvador ◽  
Colleen McKenna ◽  
Susannah Scaroni ◽  
Alexander Ulanov ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Myofibrillar Protein ◽  
Post Exercise ◽  
Exercise Muscle ◽  
Amino Acid Concentrations ◽  
Myofibrillar Protein Synthesis ◽  
Stimulation Of

Abstract Objectives Healthy eating patterns consist of eating whole foods as opposed to single nutrients. The maintenance of skeletal muscle mass is of particular interest to overall health. As such, there is a need to underpin the role of eating nutrients within their natural whole-food matrix versus isolated nutrients on the regulation of postprandial muscle protein synthesis rates. This study assessed the effects of eating salmon, a potential food within a healthy Mediterranean style eating pattern, on the stimulation of post-exercise muscle protein synthesis rates versus eating these same nutrients in isolation in healthy young adults. Methods In a crossover design, 10 recreationally active adults (24 ± 4 y; 5 M, 5 F) performed an acute bout of resistance exercise followed by the ingestion of salmon (SAL) (20.5 g protein and 7.5 g fat) or its matched constituents in the form of crystalline amino acids and fish oil (ISO). Blood and muscle biopsies were collected at rest and after exercise at 2 and 5 h during primed continuous infusions of L-[ring-2H5]phenylalanine for the measurement of myofibrillar protein synthesis and plasma amino acid profiles. Data were analyzed by using a 2-factor (time × condition) repeated-measures ANOVA with Tukey's post hoc test. Results Plasma essential amino acid concentrations increased to a similar extent in both SAL and ISO during the postprandial period (P &gt; 0.05). Likewise, postprandial plasma leucine concentrations did not differ between nutrient condition (P &gt; 0.05). The post-exercise myofibrillar protein synthetic responses were similarly stimulated in both nutrition conditions early (0–2 h; 0.079 ± 0.039%/h (SAL) compared to 0.071 ± 0.078%/h (ISO); P = 0.64) and returned to baseline later (2–5 h; 0.046 ± 0.020%/h (SAL) compared to 0.038 ± 0.025%/h (ISO); P = 0.90). Similarly, there were no differences in the stimulation of myofibrillar protein synthesis rates between SAL and ISO during the entire 0–5 h recovery period (0.058 ± 0.024%/h compared to 0.045 ± 0.027%/h, respectively; P = 0.66). Conclusions We show that the ingestion of salmon or its isolated nutrients increases plasma amino acid concentrations and enhances the stimulation of post-exercise muscle protein synthesis rates with no differences in the temporal or cumulative responses in healthy young adults. Funding Sources USDA National Institute of Food and Agriculture Hatch project.

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