Skip to main content
SpringerLink
Log in

Branched Chain Amino Acids and Muscle Atrophy Protection

  • Chapter
  • First Online:
Branched Chain Amino Acids in Clinical Nutrition

Part of the book series: Nutrition and Health ((NH))

Abstract

A variety of diseases and conditions result in muscle atrophy. Muscle atrophy causes a decrease of mobility, increased susceptibility to injuries and reduced Quality of Life (QOL). The various types of muscle atrophy are due to increased protein breakdown, decreased protein synthesis or both. Muscle mass is maintained by the balance between muscle protein synthesis and degradation.

To prevent muscle atrophy, several types of intervention have been tried. Branched-chain amino acid (BCAA) administration is one of the interventions because BCAAs have been reported to stimulate protein synthesis and attenuate protein degradation in muscles. BCAAs are components of proteins that also function as signals that regulate cellular signaling pathways activated in the protein synthesis and protein degradation. In this review, the regulatory functions of the BCAAs in cellular signaling are discussed first, and the effects of the BCAAs on several types of muscle atrophy in human and animals are described thereafter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Dodd KM, Tee AR. Leucine and mTORC1: a complex relationship. Am J Physiol Endocrinol Metab. 2012; 302:E1329–42.

    Article  CAS  PubMed  Google Scholar 

  2. Loewith R, Jacinto E, Wullschleger S, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell. 2002;10:457–68.

    Article  CAS  PubMed  Google Scholar 

  3. Suzuki T, Inoki K. Spatial regulation of the mTORC1 system in amino acids sensing pathway. Acta Biochim Biophys Sin (Shanghai). 2011;43:671–9.

    Article  CAS  Google Scholar 

  4. Fulks RM, Li JB, Goldberg AL. Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. J Biol Chem. 1975;250:290–8.

    CAS  PubMed  Google Scholar 

  5. Buse MG, Reid SS. Leucine. A possible regulator of protein turnover in muscle. J Clin Invest. 1975;56:1250–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Nobukuni T, Joaquin M, Roccio M, et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A. 2005;102:14238–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Gulati P, Gaspers LD, Dann SG, et al. Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell Metab. 2008;7:456–65.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Findlay GM, Yan L, Procter J, Mieulet V, Lamb RF. A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J. 2007;403:13–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Sancak Y, Peterson TR, Shaul YD, et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008;320:1496–501.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294:1704–8.

    Article  CAS  PubMed  Google Scholar 

  11. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 2001;98:14440–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Tintignac LA, Lagirand J, Batonnet S, Sirri V, Leibovitch MP, Leibovitch SA. Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. J Biol Chem. 2005;280:2847–56.

    Article  CAS  PubMed  Google Scholar 

  13. Csibi A, Cornille K, Leibovitch MP, et al. The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse. PLoS One. 2010;5:e8994.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Kandarian SC, Jackman RW. Intracellular signaling during skeletal muscle atrophy. Muscle Nerve. 2006;33: 155–65.

    Article  CAS  PubMed  Google Scholar 

  15. Cohen S, Brault JJ, Gygi SP, et al. During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol. 2009;185:1083–95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Lum JJ, Bauer DE, Kong M, et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 2005;120:237–48.

    Article  CAS  PubMed  Google Scholar 

  17. Schiaffino S, Hanzlikova V. Studies on the effect of denervation in developing muscle. II The lysosomal system. J Ultrastruct Res. 1972;39:1–14.

    Article  CAS  PubMed  Google Scholar 

  18. Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19:5720–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004; 15:1101–11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Sugawara T, Ito Y, Nishizawa N, Nagasawa T. Regulation of muscle protein degradation, not synthesis, by dietary leucine in rats fed a protein-deficient diet. Amino Acids. 2009;37:609–16.

    Article  CAS  PubMed  Google Scholar 

  21. Maki T, Yamamoto D, Nakanishi S, et al. Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats. Nutr Res. 2012;32:676–83.

    Article  CAS  PubMed  Google Scholar 

  22. Ono Y, Torii F, Ojima K, et al. Suppressed disassembly of autolyzing p94/CAPN3 by N2A connectin/titin in a genetic reporter system. J Biol Chem. 2006;281:18519–31.

    Article  CAS  PubMed  Google Scholar 

  23. Smith IJ, Lecker SH, Hasselgren PO. Calpain activity and muscle wasting in sepsis. Am J Physiol Endocrinol Metab. 2008;295:E762–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Hayashi K, Tada O, Higuchi K, Ohtsuka A. Effects of corticosterone on connectin content and protein breakdown in rat skeletal muscle. Biosci Biotechnol Biochem. 2000;64:2686–8.

    Article  CAS  PubMed  Google Scholar 

  25. Evans K, Nasim Z, Brown J, et al. Acidosis-sensing glutamine pump SNAT2 determines amino acid levels and mammalian target of rapamycin signalling to protein synthesis in L6 muscle cells. J Am Soc Nephrol. 2007; 18:1426–36.

    Article  CAS  PubMed  Google Scholar 

  26. Nicklin P, Bergman P, Zhang B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009;136:521–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Steffen JM, Musacchia XJ. Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids. Am J Physiol. 1986;251:R1059–63.

    CAS  PubMed  Google Scholar 

  28. Fitts RH, Riley DR, Widrick JJ. Physiology of a microgravity environment invited review: microgravity and skeletal muscle. J Appl Physiol. 2000;89:823–39.

    CAS  PubMed  Google Scholar 

  29. Thomason DB, Booth FW. Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol. 1990;68:1–12.

    Article  CAS  PubMed  Google Scholar 

  30. Desplanches D, Mayet MH, Sempore B, Flandrois R. Structural and functional responses to prolonged hindlimb suspension in rat muscle. J Appl Physiol. 1987;63:558–63.

    CAS  PubMed  Google Scholar 

  31. Kelleher AR, Kimball SR, Dennis MD, Schilder RJ, Jefferson LS. The mTORC1 signaling repressors REDD1/2 are rapidly induced and activation of p70S6K1 by leucine is defective in skeletal muscle of an immobilized rat hindlimb. Am J Physiol Endocrinol Metab. 2013;304:E229–36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. McGhee NK, Jefferson LS, Kimball SR. Elevated corticosterone associated with food deprivation upregulates expression in rat skeletal muscle of the mTORC1 repressor, REDD1. J Nutr. 2009;139:828–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Bajotto G, Sato Y, Kitaura Y, Shimomura Y. Effect of branched-chain amino acid supplementation during unloading on regulatory components of protein synthesis in atrophied soleus muscles. Eur J Appl Physiol. 2011;111:1815–28.

    Article  CAS  PubMed  Google Scholar 

  34. Herningtyas EH, Okimura Y, Handayaningsih AE, et al. Branched-chain amino acids and arginine suppress MaFbx/atrogin-1 mRNA expression via mTOR pathway in C2C12 cell line. Biochim Biophys Acta. 2008;1780:1115–20.

    Article  CAS  PubMed  Google Scholar 

  35. Paddon-Jones D, Sheffield-Moore M, Urban RJ, et al. Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab. 2004;89:4351–8.

    Article  CAS  PubMed  Google Scholar 

  36. Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW. Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol (Oxf). 2007;191:147–59.

    Article  CAS  Google Scholar 

  37. Argiles JM. Cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9 Suppl 2:S39–50.

    Article  PubMed  Google Scholar 

  38. Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss. Cancer Res. 2005;65:277–83.

    Article  CAS  PubMed  Google Scholar 

  39. May PE, Barber A, D’Olimpio JT, Hourihane A, Abumrad NN. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg. 2002;183:471–9.

    Article  CAS  PubMed  Google Scholar 

  40. Vary TC, Kimball SR. Sepsis-induced changes in protein synthesis: differential effects on fast- and slow-twitch muscles. Am J Physiol. 1992;262:C1513–9.

    CAS  PubMed  Google Scholar 

  41. Frost RA, Lang CH. mTor signaling in skeletal muscle during sepsis and inflammation: where does it all go wrong? Physiology (Bethesda). 2011;26:83–96.

    Article  CAS  Google Scholar 

  42. Lang CH, Frost RA. Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscle. J Cell Physiol. 2005;203:144–55.

    Article  CAS  PubMed  Google Scholar 

  43. Yamamoto D, Maki T, Herningtyas EH, et al. Branched-chain amino acids protect against dexamethasone-induced soleus muscle atrophy in rats. Muscle Nerve. 2010;41:819–27.

    Article  CAS  PubMed  Google Scholar 

  44. Shimizu N, Yoshikawa N, Ito N, et al. Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle. Cell Metab. 2011;13:170–82.

    Article  CAS  PubMed  Google Scholar 

  45. Gray S, Wang B, Orihuela Y, et al. Regulation of gluconeogenesis by Kruppel-like factor 15. Cell Metab. 2007;5:305–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Wang H, Kubica N, Ellisen LW, Jefferson LS, Kimball SR. Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1. J Biol Chem. 2006;281:39128–34.

    Article  CAS  PubMed  Google Scholar 

  47. Kim HK, Suzuki T, Saito K, et al. Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial. J Am Geriatr Soc. 2012;60:16–23.

    Article  PubMed  Google Scholar 

  48. Verhoeven S, Vanschoonbeek K, Verdijk LB, et al. Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. Am J Clin Nutr. 2009;89:1468–75.

    Article  CAS  PubMed  Google Scholar 

  49. Tieland M, Dirks ML, van der Zwaluw N, et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2012;13:713–9.

    Article  PubMed  Google Scholar 

  50. Malafarina V, Uriz-Otano F, Iniesta R, Gil-Guerrero L. Effectiveness of nutritional supplementation on muscle mass in treatment of sarcopenia in old age: a systematic review. J Am Med Dir Assoc. 2013;14:10–7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition and Food Science, Kobe Women’s University Graduate School of Life Sciences, 2-1 Higashi Suma Aoyama, Suma-ku, Kobe, Japan

    Yasuhiko Okimura M.D., Ph.D.

Authors
  1. Yasuhiko Okimura M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhiko Okimura M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Intensive Care, Barnet and Chase Farm Hospitals, Royal Free London NHS Foundation Trust, London, United Kingdom

    Rajkumar Rajendram

  2. Diabetes and Nutritional Sciences, Kings College London, London, United Kingdom

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Okimura, Y. (2015). Branched Chain Amino Acids and Muscle Atrophy Protection. In: Rajendram, R., Preedy, V., Patel, V. (eds) Branched Chain Amino Acids in Clinical Nutrition. Nutrition and Health. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1914-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1914-7_4

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1913-0

  • Online ISBN: 978-1-4939-1914-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation