scholarly journals Leucine-enriched amino acids maintain peripheral mTOR-Rheb localization independent of myofibrillar protein synthesis and mTORC1 signaling postexercise

2020 ◽  
Vol 129 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Sarkis J. Hannaian ◽  
Nathan Hodson ◽  
Sidney Abou Sawan ◽  
Michael Mazzulla ◽  
Hiroyuki Kato ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Protein Interactions ◽  
Human Skeletal Muscle ◽  
Myofibrillar Protein ◽  
Protein Protein Interactions ◽  
Peripheral Location ◽  
Mtorc1 Signaling ◽  
Myofibrillar Protein Synthesis

This is the first study to investigate whether postexercise leucine-enriched amino acid (LEAA) ingestion elevates mTORC1 translocation and protein-protein interactions in human skeletal muscle. Here, we observed that although LEAA ingestion did not further elevate postexercise MyoPS or mTORC1 signaling compared with placebo, mTORC1 peripheral location and interaction with Rheb were maintained. This may serve to “prime” mTORC1 for subsequent anabolic stimuli.

scholarly journals Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

2009 ◽  
Vol 106 (4) ◽  
pp. 1374-1384 ◽  
Author(s):  
Micah J. Drummond ◽  
Hans C. Dreyer ◽  
Christopher S. Fry ◽  
Erin L. Glynn ◽  
Blake B. Rasmussen
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Essential Amino Acids ◽  
Skeletal Muscle Protein ◽  
Mtorc1 Signaling

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise

2014 ◽  
Vol 307 (1) ◽  
pp. E71-E83 ◽  
Author(s):  
Tyler A. Churchward-Venne ◽  
Lisa M. Cotie ◽  
Maureen J. MacDonald ◽  
Cameron J. Mitchell ◽  
Todd Prior ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Blood Flow ◽  
Protein Synthesis ◽  
Whey Protein ◽  
Myofibrillar Protein ◽  
Microvascular Perfusion ◽  
Anabolic Resistance ◽  
Nonessential Amino Acids ◽  
Myofibrillar Protein Synthesis

Aging is associated with anabolic resistance, a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signaling through mTORC1. Twenty-one elderly males (65–80 yr) completed acute unilateral resistance exercise prior to being assigned to ingest a high dose (45 g) of whey protein (WHEY) or a low dose (15 g) of whey protein with 10 g of citrulline (WHEY + CIT) or with 10 g of nonessential amino acids (WHEY + NEAA). A primed, continuous infusion of l-[ ring-13C6] phenylalanine with serial muscle biopsies was used to measure MPS and protein phosphorylation, whereas ultrasound was used to measure microvascular circulation under basal and postprandial conditions in both a rested (FED) and exercised (EX-FED) leg. Argininemia was greater in WHEY + CIT vs. WHEY and WHEY + NEAA from 30 to 300 min postexercise ( P < 0.001), but there were no treatment differences in blood flow or microvascular perfusion (all P > 0.05). Phosphorylation of p70S6K-Thr389was greater in WHEY vs. WHEY + NEAA ( P = 0.02). Postprandial MPS was greater in WHEY vs. WHEY + CIT and WHEY + NEAA under both FED (WHEY: ∼128%; WHEY + CIT: ∼56%; WHEY + NEAA: ∼38%) and EX-FED (WHEY: ∼251%; WHEY + CIT: ∼124%; WHEY + NEAA: ∼108%) conditions ( P = 0.003). Citrulline coingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared with nonessential amino acids.

scholarly journals Presleep dietary protein-derived amino acids are incorporated in myofibrillar protein during postexercise overnight recovery

2018 ◽  
Vol 314 (5) ◽  
pp. E457-E467 ◽  
Author(s):  
Jorn Trommelen ◽  
Imre W. K. Kouw ◽  
Andrew M. Holwerda ◽  
Tim Snijders ◽  
Shona L. Halson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Dietary Protein ◽  
Myofibrillar Protein ◽  
Whole Body ◽  
Body Protein ◽  
Protein Ingestion ◽  
Casein Protein ◽  
The Impact ◽  
Myofibrillar Protein Synthesis

The purpose of this study was to determine the impact of ingesting 30 g casein protein with and without 2 g free leucine before sleep on myofibrillar protein synthesis rates during postexercise overnight recovery. Thirty-six healthy young men performed a single bout of resistance-type exercise in the evening (1945) after a full day of dietary standardization. Thirty minutes before sleep (2330), subjects ingested 30 g intrinsically l-[1-13C]phenylalanine-labeled protein with (PRO+leu, n = 12) or without (PRO, n = 12) 2 g free leucine, or a noncaloric placebo (PLA, n = 12). Continuous intravenous l-[ ring-2H5]phenylalanine, l-[1-13C]leucine, and l-[ ring-2H2]tyrosine infusions were applied. Blood and muscle tissue samples were collected to assess whole body protein net balance, myofibrillar protein synthesis rates, and overnight incorporation of dietary protein-derived amino acids into myofibrillar protein. Protein ingestion before sleep improved overnight whole body protein net balance ( P < 0.001). Myofibrillar protein synthesis rates did not differ significantly between treatments as assessed by l-[ ring-2H5]phenylalanine (0.057 ± 0.002, 0.055 ± 0.002, and 0.055 ± 0.004%/h for PLA, PRO, and PRO+leu, respectively; means ± SE; P = 0.850) or l-[1-13C]leucine (0.080 ± 0.004, 0.073 ± 0.004, and 0.083 ± 0.006%/h, respectively; P = 0.328). Myofibrillar l-[1-13C]phenylalanine enrichments increased following protein ingestion but did not differ between the PRO and PRO+leu treatments. In conclusion, protein ingestion before sleep improves whole body protein net balance and provides amino acids that are incorporated into myofibrillar protein during sleep. However, the ingestion of 30 g casein protein with or without additional free leucine before sleep does not increase muscle protein synthesis rates during postexercise overnight recovery.

scholarly journals Improved recovery from skeletal muscle damage is largely unexplained by myofibrillar protein synthesis or inflammatory and regenerative gene expression pathways

2020 ◽  
Author(s):  
George Frederick Pavis ◽  
Tom SO Jameson ◽  
Marlou L. Dirks ◽  
Benjamin P. Lee ◽  
Doaa Reda Abdelrahman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Damage ◽  
Muscle Function ◽  
Nutritional Intervention ◽  
Myofibrillar Protein ◽  
Skeletal Muscle Damage ◽  
Amino Acid Availability ◽  
Expression Pathways ◽  
Myofibrillar Protein Synthesis

The contribution of myofibrillar protein synthesis (MyoPS) to recovery from skeletal muscle damage in humans is unknown. Recreationally active males and females consumed a daily protein-polyphenol beverage targeted at increasing amino acid availability and reducing inflammation (PPB; n=9), both known to affect MyoPS, or an isocaloric placebo (PLA; n=9) during 168 h of recovery from 300 maximal unilateral eccentric contractions (EE). Muscle function was assessed daily. Muscle biopsies were collected 24, 27, 36, 72 and 168 h for MyoPS measurements using 2H2O and expression of 224 genes using RT-qPCR and pathway analysis. PPB improved recovery of muscle function, which was impaired for five days following EE in PLA (interaction; P<0.05). Acute postprandial MyoPS rates were unaffected by nutritional intervention (24-27 h). EE increased overnight (27-36 h) MyoPS versus control leg (PLA: 33±19%; PPB: 79±25%; leg P<0.01), and PPB tended to increase this further (interaction P=0.06). Daily MyoPS rates were greater with PPB between 72-168 h after EE, albeit after function had recovered. Inflammatory and regenerative signaling pathways were dramatically upregulated and clustered following EE but were unaffected by nutritional intervention. These results suggest that accelerated recovery from EE is not explained by elevated MyoPS or suppression of inflammation.

Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle

2001 ◽  
Vol 281 (3) ◽  
pp. E466-E471 ◽  
Author(s):  
Jeffrey S. Greiwe ◽  
Guim Kwon ◽  
Michael L. McDaniel ◽  
Clay F. Semenkovich
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
S6 Kinase ◽  
Signaling Mechanism ◽  
Insulin Resistant ◽  
Branched Chain ◽  
Plasma Leucine

Amino acids and insulin have anabolic effects in skeletal muscle, but the mechanisms are poorly understood. To test the hypothesis that leucine and insulin stimulate translation initiation in human skeletal muscle by phosphorylating 70-kDa ribosomal protein S6 kinase (p70S6k), we infused healthy adults with leucine alone ( n = 6), insulin alone ( n= 6), or both leucine and insulin ( n = 6) for 2 h. p70S6k and protein kinase B (PKB) serine473phosphorylation were measured in vastus lateralis muscles. Plasma leucine increased from ∼116 to 343 μmol/l during the leucine-alone and leucine + insulin infusions. Plasma insulin increased to ∼400 pmol/l during the insulin-alone and leucine + insulin infusions and was unchanged during the leucine-alone infusion. Phosphorylation of p70S6k increased 4-fold in response to leucine alone, 8-fold in response to insulin alone, and 18-fold after the leucine + insulin infusion. Insulin-alone and leucine + insulin infusions increased PKB phosphorylation, but leucine alone had no effect. These results show that physiological concentrations of leucine and insulin activate a key mediator of protein synthesis in human skeletal muscle. They suggest that leucine stimulates protein synthesis through a nutrient signaling mechanism independent of insulin, raising the possibility that administration of branched-chain amino acids may improve protein synthesis in insulin-resistant states.

Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle

1995 ◽  
Vol 268 (1) ◽  
pp. E75-E84 ◽  
Author(s):  
G. Biolo ◽  
R. Y. Fleming ◽  
S. P. Maggi ◽  
R. R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Human Skeletal Muscle ◽  
De Novo ◽  
Transmembrane Transport ◽  
Acid Transport ◽  
De Novo Synthesis ◽  
Intracellular Amino Acid

We have used stable isotopic tracers of amino acids to measure in vivo transmembrane transport of phenylalanine, leucine, lysine, alanine, and glutamine as well as the rates of intracellular amino acid appearance from proteolysis, de novo synthesis, and disappearance to protein synthesis in human skeletal muscle. Calculations were based on data obtained by the arteriovenous catheterization of the femoral vessels and muscle biopsy. We found that the fractional contribution of transport from the bloodstream to the total intracellular amino acid appearance depends on the individual amino acid, varying between 0.63 +/- 0.02 for phenylalanine and 0.22 +/- 0.02 for alanine. Rates of alanine and glutamine de novo synthesis were approximately eight and five times their rate of appearance from protein breakdown, respectively. The model-derived rate of protein synthesis was highly correlated with the same value calculated by means of the tracer incorporation technique. Furthermore, amino acid transport rates were in the range expected from literature values. Consequently, we conclude that our new model provides a valid means of quantifying the important aspects of protein synthesis, breakdown, and amino acid transport in human subjects.

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