Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle

Resistance exercise and amino acids are two major factors that influence muscle protein turnover. Here, we examined the effects of resistance exercise and branched-chain amino acids (BCAA), individually and in combination, on the expression of anabolic and catabolic genes in human skeletal muscle. Seven subjects performed two sessions of unilateral leg press exercise with randomized supplementation with BCAA or flavored water. Biopsies were collected from the vastus lateralis muscle of both the resting and exercising legs before and repeatedly after exercise to determine levels of mRNA, protein phosphorylation, and amino acid concentrations. Intake of BCAA reduced ( P < 0.05) MAFbx mRNA by 30 and 50% in the resting and exercising legs, respectively. The level of MuRF-1 mRNA was elevated ( P < 0.05) in the exercising leg two- and threefold under the placebo and BCAA conditions, respectively, whereas MuRF-1 total protein increased by 20% ( P < 0.05) only in the placebo condition. Phosphorylation of p70S6k increased to a larger extent (∼2-fold; P < 0.05) in the early recovery period with BCAA supplementation, whereas the expression of genes regulating mTOR activity was not influenced by BCAA. Muscle levels of phenylalanine and tyrosine were reduced (13–17%) throughout recovery ( P < 0.05) in the placebo condition and to a greater extent (32–43%; P < 0.05) following BCAA supplementation in both resting and exercising muscle. In conclusion, BCAA ingestion reduced MAFbx mRNA and prevented the exercise-induced increase in MuRF-1 total protein in both resting and exercising leg. Further-more, resistance exercise differently influenced MAFbx and MuRF-1 mRNA expression, suggesting both common and divergent regulation of these two ubiquitin ligases.

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BCAA intake affects protein metabolism in muscle after but not during exercise in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.2.e365 ◽

2001 ◽

Vol 281 (2) ◽

pp. E365-E374 ◽

Cited By ~ 48

Author(s):

Eva Blomstrand ◽

Bengt Saltin

Keyword(s):

Amino Acids ◽

Recovery Period ◽

Aromatic Amino Acids ◽

Branched Chain Amino Acids ◽

Cycle Exercise ◽

Placebo Condition ◽

Muscle Concentration ◽

Branched Chain ◽

Sparing Effect ◽

Exercise In Humans

Branched-chain amino acids (BCAA) or a placebo was given to seven subjects during 1 h of ergometer cycle exercise and a 2-h recovery period. Intake of BCAA did not influence the rate of exchange of the aromatic amino acids, tyrosine and phenylalanine, in the legs during exercise or the increase in their concentration in muscle. The increase was ∼30% in both conditions. On the other hand, in the recovery period after exercise, a faster decrease in the muscle concentration of aromatic amino acids was found in the BCAA experiment (46% compared with 25% in the placebo condition). There was also a tendency to a smaller release (an average of 32%) of these amino acids from the legs during the 2-h recovery. The results suggest that BCAA have a protein-sparing effect during the recovery after exercise, either that protein synthesis has been stimulated and/or protein degradation has decreased, but the data during exercise are too variable to make any conclusions about the effects during exercise. The effect in the recovery period does not seem to be mediated by insulin.

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Branched-chain amino acids increase p70S6k phosphorylation in human skeletal muscle after resistance exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00430.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. E1-E7 ◽

Cited By ~ 166

Author(s):

Håkan K. R. Karlsson ◽

Per-Anders Nilsson ◽

Johnny Nilsson ◽

Alexander V. Chibalin ◽

Juleen R. Zierath ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Protein Kinase ◽

Resistance Exercise ◽

P38 Mapk ◽

Recovery Period ◽

Plasma Concentrations ◽

Branched Chain Amino Acids ◽

Mitogen Activated Protein Kinase ◽

Branched Chain

The aim of the study was to investigate the effect of resistance exercise alone or in combination with oral intake of branched-chain amino acids (BCAA) on phosphorylation of the 70-kDa S6 protein kinase (p70S6k) and mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK1/2), and p38 MAPK in skeletal muscle. Seven male subjects performed one session of quadriceps muscle resistance training (4 × 10 repetitions at 80% of one repetition maximum) on two occasions. In a randomized order, double-blind, crossover test, subjects ingested a solution of BCAA or placebo during and after exercise. Ingestion of BCAA increased plasma concentrations of isoleucine, leucine, and valine during exercise and throughout recovery after exercise (2 h postexercise), whereas no change was noted after the placebo trial. Resistance exercise led to a robust increase in p70S6k phosphorylation at Ser424 and/or Thr421, which persisted 1 and 2 h after exercise. BCAA ingestion further enhanced p70S6k phosphorylation 3.5-fold during recovery. p70S6k phosphorylation at Thr389 was unaltered directly after resistance exercise. However, during recovery, Thr389 phosphorylation was profoundly increased, but only during the BCAA trial. Furthermore, phosphorylation of the ribosomal protein S6 was also increased in the recovery period only during the BCAA trial. Exercise led to a marked increase in ERK1/2 and p38 MAPK phosphorylation, which was completely suppressed upon recovery and unaltered by BCAA. In conclusion, BCAA, ingested during and after resistance exercise, mediate signal transduction through p70S6k in skeletal muscle.

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Branched-chain amino acids do not improve muscle recovery from resistance exercise in untrained young adults

Amino Acids ◽

10.1007/s00726-019-02776-5 ◽

2019 ◽

Vol 51 (9) ◽

pp. 1387-1395 ◽

Cited By ~ 1

Author(s):

José Maria Estoche ◽

Jeferson Lucas Jacinto ◽

Mirela Casonato Roveratti ◽

Juliano Moro Gabardo ◽

Cosme Franklim Buzzachera ◽

...

Keyword(s):

Amino Acids ◽

Young Adults ◽

Resistance Exercise ◽

Branched Chain Amino Acids ◽

Muscle Recovery ◽

Branched Chain

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Can nutritional criteria help predict outcome in hospitalized patients?

Clinical Chemistry ◽

10.1093/clinchem/32.11.2077 ◽

1986 ◽

Vol 32 (11) ◽

pp. 2077-2079 ◽

Cited By ~ 6

Author(s):

V M Prabhakaran ◽

S Pujara ◽

A J Mills ◽

V W Whalen

Keyword(s):

Amino Acids ◽

Total Protein ◽

Fatal Outcome ◽

Branched Chain Amino Acids ◽

Hospitalized Patients ◽

Predicting Outcome ◽

Branched Chain ◽

A Prospective Study ◽

Index Weight ◽

Nonessential Amino Acids

Abstract The following nutritional criteria were evaluated for their usefulness in predicting outcome in a prospective study of 66 randomly selected hospitalized patients with a variety of diagnoses: total protein, albumin, and transferrin concentrations in serum, creatinine height index, weight height index, phenylalanine/tyrosine ratio (Phe/Tyr), concentration of branched-chain amino acids in serum, and ratio of essential to nonessential amino acids in serum. The cases were followed from admission to discharge, and were classified into the following three groups: 43 "well"; 14 with "complications" but recovered; and nine "dead". Statistical analysis (Scheffe's s-test) demonstrated the means of "well" and "dead" groups to be different for total protein, albumin, transferrin, and Phe/Tyr. In individual patients the nutritional criteria, even for those with fatal outcome, were poor indicators of outcome. These nutritional criteria are useful in identifying hospitalized groups that are at maximum risk (i.e., death), but are much less useful for individual patients.

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Associations between Plasma Branched Chain Amino Acids and Health Biomarkers in Response to Resistance Exercise Training Across Age

Nutrients ◽

10.3390/nu12103029 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3029

Author(s):

Mariwan H. Sayda ◽

Bethan E. Phillips ◽

John P. Williams ◽

Paul L. Greenhaff ◽

Daniel J. Wilkinson ◽

...

Keyword(s):

Amino Acids ◽

Exercise Training ◽

Resistance Exercise ◽

Branched Chain Amino Acids ◽

Metabolic Health ◽

Whole Body ◽

Gas Chromatography Mass Spectrometry ◽

Resistance Exercise Training ◽

Fasting Plasma ◽

Branched Chain

Leucine, isoleucine and valine (i.e., the branched chain amino acids, BCAA) play a key role in the support of tissue protein regulation and can be mobilized as energy substrates during times of starvation. However, positive relationships exist between elevated levels of BCAA and insulin resistance (IR). Thus, we sought to investigate the links between fasting plasma BCAA following a progressive resistance exercise training (RET) programme, an intervention known to improve metabolic health. Fasting plasma BCAA were quantified in adults (young: 18–28 y, n = 8; middle-aged: 45–55 y, n = 9; older: 65–75 y, n = 15; BMI: 23–28 kg/m2, both males and females (~50:50), in a cross-sectional, intervention study. Participants underwent 20-weeks whole-body RET. Measurements of body composition, muscle strength (1-RM) and metabolic health biomarkers (e.g., HOMA-IR) were made at baseline and post-RET. BCAA concentrations were determined by gas-chromatography mass spectrometry (GC-MS). No associations were observed across age with BCAA; however, RET elicited (p < 0.05) increases in plasma BCAA (all age-groups), while HOMA-IR scores reduced (p < 0.05) following RET. After RET, positive correlations in lean body mass (p = 0.007) and strength gains (p = 0.001) with fasting BCAA levels were observed. Elevated BCAA are not a robust marker of ageing nor IR in those with a healthy BMI; rather, despite decreasing IR, RET was associated with increased BCAA.

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Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids

Biochemical Journal ◽

10.1042/bj2540579 ◽

1988 ◽

Vol 254 (2) ◽

pp. 579-584 ◽

Cited By ~ 209

Author(s):

P J Garlick ◽

I Grant

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Branched Chain Amino Acids ◽

Acid Infusion ◽

Amino Acid Infusion ◽

Branched Chain

Rates of muscle protein synthesis were measured in vivo in tissues of post-absorptive young rats that were given intravenous infusions of various combinations of insulin and amino acids. In the absence of amino acid infusion, there was a steady rise in muscle protein synthesis with plasma insulin concentration up to 158 mu units/ml, but when a complete amino acids mixtures was included maximal rates were obtained at 20 mu units/ml. The effect of the complete mixture could be reproduced by a mixture of essential amino acids or of branched-chain amino acids, but not by a non-essential mixture, alanine, methionine or glutamine. It is concluded that amino acids, particularly the branched-chain ones, increase the sensitivity of muscle protein synthesis to insulin.

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Effect of endurance training and branched-chain amino acids on the signaling for muscle protein synthesis in CKD model rats fed a low-protein diet

AJP Renal Physiology ◽

10.1152/ajprenal.00592.2015 ◽

2017 ◽

Vol 313 (3) ◽

pp. F805-F814 ◽

Cited By ~ 3

Author(s):

Takuya Yoshida ◽

Sachika Kakizawa ◽

Yuri Totsuka ◽

Miho Sugimoto ◽

Shinji Miura ◽

...

Keyword(s):

Amino Acids ◽

Renal Function ◽

Protein Synthesis ◽

Sham Group ◽

Treadmill Exercise ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Branched Chain Amino Acids ◽

Low Protein ◽

Branched Chain

A low-protein diet (LPD) protects against the progression of renal injury in patients with chronic kidney disease (CKD). However, LPD may accelerate muscle wasting in these patients. Both exercise and branched-chain amino acids (BCAA) are known to increase muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) pathway. The aim of this study was to investigate whether endurance exercise and BCAA play a role for increasing muscle protein synthesis in LPD-fed CKD (5/6 nephrectomized) rats. Both CKD and sham rats were pair-fed on LPD or LPD fortified with a BCAA diet (BD), and approximately one-half of the animals in each group was subjected to treadmill exercise (15 m/min, 1 h/day, 5 days/wk). After 7 wk, renal function was measured, and soleus muscles were collected to evaluate muscle protein synthesis. Renal function did not differ between LPD- and BD-fed CKD rats, and the treadmill exercise did not accelerate renal damage in either group. The treadmill exercise slightly increased the phosphorylation of p70s6 kinase, a marker of mTOR activity, in the soleus muscle of LPD-fed CKD rats compared with the sham group. Furthermore, BCAA supplementation of the LPD-fed, exercise-trained CKD rats restored the phosphorylation of p70s6 kinase to the same level observed in the sham group; however, the corresponding induced increase in muscle protein synthesis and muscle mass was marginal. These results indicate that the combination of treadmill exercise and BCAA stimulates cell signaling to promote muscle protein synthesis; however, the implications of this effect for muscle growth remain to be clarified.

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