Branched-chain amino acids as fuels and anabolic signals in human muscle

M J Rennie, J Bohe, K Smith, H Wackerhage, P Greenhaff

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

During exercise, there is an increase in amino acid (AA) oxidation accompanied by a depression in whole-body protein synthesis and an increase in protein breakdown. Leucine oxidation increases in proportion to energy expenditure, but the total contribution of BCAA to fuel provision during exercise is minor and insufficient to increase dietary protein requirements. When investigating the effects of AA on the control of muscle protein synthesis (MPS), we showed that increased availability of mixed AAs caused a rise in human MPS to about the same extent as complete meals. Leucine alone (and to some extent other essential, but not nonessential, AAs) can stimulate MPS for a short period, suggesting that leucine acts as a signal as well as a substrate. MPS stimulation by infused AAs shows tachyphylaxis, returning to basal rates after 2 h, possibly explaining why chronically elevated leucine delivery does not elevate MPS clinically. Increased availability of essential amino acids (EAAs) results in dose-related responses of MPS, but, in elderly subjects, there is blunted sensitivity and responsiveness associated with decreased total RNA and mRNA for signaling proteins and signaling activity. Increases of MPS due to EAAs are associated with elevation of signaling activity in the mammalian target of rapamycin (mTOR)/p70 ribosomal subunit S6 kinase eukaryotic initiation factor 4 binding protein 1 pathway, without requiring rises of plasma insulin availability above 10 mu U/mL. However, at insulin of < 5 mu U/mL, AAs appear to stimulate MPS without increasing mTOR signaling. Further increasing availability of insulin to postprandial values increases signaling activity, but has no further effect on MPS.

Original languageEnglish
Number of pages5
JournalThe Journal of Nutrition
Volume136
Publication statusPublished - 2006

Keywords

  • protein
  • fuel
  • protein turnover
  • muscle
  • HUMAN SKELETAL-MUSCLE
  • PROTEIN-SYNTHESIS
  • PHYSIOLOGICAL HYPERINSULINEMIA
  • DIETARY-PROTEIN
  • TURNOVER
  • EXERCISE
  • INFUSION
  • LEUCINE
  • <1-C-13>LEUCINE
  • METABOLISM

Cite this

Rennie, M. J., Bohe, J., Smith, K., Wackerhage, H., & Greenhaff, P. (2006). Branched-chain amino acids as fuels and anabolic signals in human muscle. The Journal of Nutrition, 136.

Branched-chain amino acids as fuels and anabolic signals in human muscle. / Rennie, M J ; Bohe, J ; Smith, K ; Wackerhage, H ; Greenhaff, P .

In: The Journal of Nutrition, Vol. 136, 2006.

Research output: Contribution to journalArticle

Rennie, MJ, Bohe, J, Smith, K, Wackerhage, H & Greenhaff, P 2006, 'Branched-chain amino acids as fuels and anabolic signals in human muscle', The Journal of Nutrition, vol. 136.
Rennie MJ, Bohe J, Smith K, Wackerhage H, Greenhaff P. Branched-chain amino acids as fuels and anabolic signals in human muscle. The Journal of Nutrition. 2006;136.
Rennie, M J ; Bohe, J ; Smith, K ; Wackerhage, H ; Greenhaff, P . / Branched-chain amino acids as fuels and anabolic signals in human muscle. In: The Journal of Nutrition. 2006 ; Vol. 136.
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N2 - During exercise, there is an increase in amino acid (AA) oxidation accompanied by a depression in whole-body protein synthesis and an increase in protein breakdown. Leucine oxidation increases in proportion to energy expenditure, but the total contribution of BCAA to fuel provision during exercise is minor and insufficient to increase dietary protein requirements. When investigating the effects of AA on the control of muscle protein synthesis (MPS), we showed that increased availability of mixed AAs caused a rise in human MPS to about the same extent as complete meals. Leucine alone (and to some extent other essential, but not nonessential, AAs) can stimulate MPS for a short period, suggesting that leucine acts as a signal as well as a substrate. MPS stimulation by infused AAs shows tachyphylaxis, returning to basal rates after 2 h, possibly explaining why chronically elevated leucine delivery does not elevate MPS clinically. Increased availability of essential amino acids (EAAs) results in dose-related responses of MPS, but, in elderly subjects, there is blunted sensitivity and responsiveness associated with decreased total RNA and mRNA for signaling proteins and signaling activity. Increases of MPS due to EAAs are associated with elevation of signaling activity in the mammalian target of rapamycin (mTOR)/p70 ribosomal subunit S6 kinase eukaryotic initiation factor 4 binding protein 1 pathway, without requiring rises of plasma insulin availability above 10 mu U/mL. However, at insulin of < 5 mu U/mL, AAs appear to stimulate MPS without increasing mTOR signaling. Further increasing availability of insulin to postprandial values increases signaling activity, but has no further effect on MPS.

AB - During exercise, there is an increase in amino acid (AA) oxidation accompanied by a depression in whole-body protein synthesis and an increase in protein breakdown. Leucine oxidation increases in proportion to energy expenditure, but the total contribution of BCAA to fuel provision during exercise is minor and insufficient to increase dietary protein requirements. When investigating the effects of AA on the control of muscle protein synthesis (MPS), we showed that increased availability of mixed AAs caused a rise in human MPS to about the same extent as complete meals. Leucine alone (and to some extent other essential, but not nonessential, AAs) can stimulate MPS for a short period, suggesting that leucine acts as a signal as well as a substrate. MPS stimulation by infused AAs shows tachyphylaxis, returning to basal rates after 2 h, possibly explaining why chronically elevated leucine delivery does not elevate MPS clinically. Increased availability of essential amino acids (EAAs) results in dose-related responses of MPS, but, in elderly subjects, there is blunted sensitivity and responsiveness associated with decreased total RNA and mRNA for signaling proteins and signaling activity. Increases of MPS due to EAAs are associated with elevation of signaling activity in the mammalian target of rapamycin (mTOR)/p70 ribosomal subunit S6 kinase eukaryotic initiation factor 4 binding protein 1 pathway, without requiring rises of plasma insulin availability above 10 mu U/mL. However, at insulin of < 5 mu U/mL, AAs appear to stimulate MPS without increasing mTOR signaling. Further increasing availability of insulin to postprandial values increases signaling activity, but has no further effect on MPS.

KW - protein

KW - fuel

KW - protein turnover

KW - muscle

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KW - TURNOVER

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KW - INFUSION

KW - LEUCINE

KW - <1-C-13>LEUCINE

KW - METABOLISM

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JO - The Journal of Nutrition

JF - The Journal of Nutrition

SN - 0022-3166

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