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Anabolic Resistance

  • Jean-Paul ThissenEmail author
Chapter

Abstract

Muscle atrophy is the hallmark of several catabolic conditions. Whatever the cause, the skeletal muscle loss is associated with comorbidities and poor survival. The mass of the skeletal muscle is maintained normally by equilibrium between protein synthesis and breakdown. Rate of synthesis in particular is positively regulated by nutrition and exercise. Anabolic resistance can be defined as a situation where the skeletal muscle is unable to respond appropriately to these anabolic stimuli by stimulating protein synthesis. Anabolic resistance contributes to muscle mass loss in elderly, during immobilization as well as in response to inflammation and cancer. The mechanisms responsible for this blunted response to anabolic stimuli are still under investigation. Several strategies may serve to compensate for anabolic resistance. Optimization of protein intake, resistance exercise, and anti-inflammatory agents appear promising to override this anabolic resistance and mitigate its consequence, the skeletal muscle mass loss.

Keywords

Protein synthesis Protein breakdown Skeletal muscle Amino acids Insulin Critically ill 

References

  1. 1.
    Cohen S, Nathan JA, Goldberg AL (2015) Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov 14(1):58–74PubMedCrossRefGoogle Scholar
  2. 2.
    Phillips BE, Hill DS, Atherton PJ (2012) Regulation of muscle protein synthesis in humans. Curr Opin Clin Nutr Metab Care 15(1):58–63PubMedCrossRefGoogle Scholar
  3. 3.
    Gorissen SH, Remond D, Van Loon LJ (2015) The muscle protein synthetic response to food ingestion. Meat Sci 109:96–100PubMedCrossRefGoogle Scholar
  4. 4.
    Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D et al (2010) Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. Am J Clin Nutr 92(5):1080–1088PubMedCrossRefGoogle Scholar
  5. 5.
    Dideriksen K, Reitelseder S, Holm L (2013) Influence of amino acids, dietary protein, and physical activity on muscle mass development in humans. Nutrients 5(3):852–876PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Deutz NE, Wolfe RR (2013) Is there a maximal anabolic response to protein intake with a meal? Clin Nutr 32(2):309–313PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Kimball SR, Jefferson LS (2006) Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. J Nutr 136(1):227S–231SPubMedGoogle Scholar
  8. 8.
    Ham DJ, Caldow MK, Lynch GS, Koopman R (2014) Leucine as a treatment for muscle wasting: a critical review. Clin Nutr 33(6):937–945PubMedCrossRefGoogle Scholar
  9. 9.
    Svanberg E, Jefferson LS, Lundholm K, Kimball SR (1997) Postprandial stimulation of muscle protein synthesis is independent of changes in insulin. Am J Physiol 272(5 Pt 1):E841–E847PubMedGoogle Scholar
  10. 10.
    Greenhaff PL, Karagounis LG, Peirce N, Simpson EJ, Hazell M, Layfield R et al (2008) Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle. Am J Physiol Endocrinol Metab 295(3):E595–E604PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Barazzoni R, Short KR, Asmann Y, Coenen-Schimke JM, Robinson MM, Nair KS (2012) Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement. Am J Physiol Endocrinol Metab 303(9):E1117–E1125PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Trommelen J, Groen BB, Hamer HM, de Groot LC, Van Loon LJ (2015) Mechanisms in Endocrinology: exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review. Eur J Endocrinol 173(1):R25–R34PubMedCrossRefGoogle Scholar
  13. 13.
    Heslin MJ, Newman E, Wolf RF, Pisters PW, Brennan MF (1992) Effect of hyperinsulinemia on whole body and skeletal muscle leucine carbon kinetics in humans. Am J Physiol 262(6 Pt 1):E911–E918PubMedGoogle Scholar
  14. 14.
    Phillips SM, Tipton KD, Aarsland A, Wolf SE, Wolfe RR (1997) Mixed muscle protein synthesis and breakdown after resistance exercise in humans. Am J Physiol 273(1 Pt 1):E99–E107PubMedGoogle Scholar
  15. 15.
    Biolo G, Tipton KD, Klein S, Wolfe RR (1997) An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. Am J Physiol Endocrinol Metab 273(1):E122–E129Google Scholar
  16. 16.
    Timmerman KL, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Jennings K et al (2012) A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults. Am J Clin Nutr 95(6):1403–1412PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Haran PH, Rivas DA, Fielding RA (2012) Role and potential mechanisms of anabolic resistance in sarcopenia. J Cachexia Sarcopenia Muscle 3(3):157–162PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Rennie MJ (2009) Anabolic resistance in critically ill patients. Crit Care Med 37(10 Suppl):S398–S399PubMedCrossRefGoogle Scholar
  19. 19.
    Rennie MJ, Selby A, Atherton P, Smith K, Kumar V, Glover EL et al (2010) Facts, noise and wishful thinking: muscle protein turnover in aging and human disuse atrophy. Scand J Med Sci Sports 20(1):5–9PubMedCrossRefGoogle Scholar
  20. 20.
    Glynn EL, Fry CS, Drummond MJ, Dreyer HC, Dhanani S, Volpi E et al (2010) Muscle protein breakdown has a minor role in the protein anabolic response to essential amino acid and carbohydrate intake following resistance exercise. Am J Physiol Regul Integr Comp Physiol 299(2):R533–R540PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Guillet C, Boirie Y, Walrand S (2004) An integrative approach to in-vivo protein synthesis measurement: from whole tissue to specific proteins. Curr Opin Clin Nutr Metab Care 7(5):531–538PubMedCrossRefGoogle Scholar
  22. 22.
    Bodine SC (2013) Disuse-induced muscle wasting. Int J Biochem Cell Biol 45(10):2200–2208PubMedCrossRefGoogle Scholar
  23. 23.
    Tanner RE, Brunker LB, Agergaard J, Barrows KM, Briggs RA, Kwon OS et al (2015) Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation. J Physiol 593(18):4259–4273PubMedCrossRefGoogle Scholar
  24. 24.
    Breen L, Phillips SM (2011) Skeletal muscle protein metabolism in the elderly: interventions to counteract the ‘anabolic resistance’ of ageing. Nutr Metab [Lond] 8:68CrossRefGoogle Scholar
  25. 25.
    Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W et al (2009) Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol 587(Pt 1):211–217PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Durham WJ, Casperson SL, Dillon EL, Keske MA, Paddon-Jones D, Sanford AP et al (2010) Age-related anabolic resistance after endurance-type exercise in healthy humans. FASEB J 24(10):4117–4127PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Volpi E, Mittendorfer B, Rasmussen BB, Wolfe RR (2000) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J Clin Endocrinol Metab 85(12):4481–4490PubMedPubMedCentralGoogle Scholar
  28. 28.
    Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P et al (2005) Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J 19(3):422–424PubMedGoogle Scholar
  29. 29.
    Wilkes EA, Selby AL, Atherton PJ, Patel R, Rankin D, Smith K et al (2009) Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia. Am J Clin Nutr 90(5):1343–1350PubMedCrossRefGoogle Scholar
  30. 30.
    Wall BT, Snijders T, Senden JM, Ottenbros CL, Gijsen AP, Verdijk LB et al (2013) Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men. J Clin Endocrinol Metab 98(12):4872–4881PubMedCrossRefGoogle Scholar
  31. 31.
    Breen L, Stokes KA, Churchward-Venne TA, Moore DR, Baker SK, Smith K et al (2013) Two weeks of reduced activity decreases leg lean mass and induces “anabolic resistance” of myofibrillar protein synthesis in healthy elderly. J Clin Endocrinol Metab 98(6):2604–2612PubMedCrossRefGoogle Scholar
  32. 32.
    Glover EI, Phillips SM, Oates BR, Tang JE, Tarnopolsky MA, Selby A et al (2008) Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion. J Physiol 586(Pt 24):6049–6061PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Steiner JL, Lang CH (2015) Sepsis attenuates the anabolic response to skeletal muscle contraction. Shock 43(4):344–351PubMedCrossRefGoogle Scholar
  34. 34.
    Vary TC, Jefferson LS, Kimball SR (2001) Insulin fails to stimulate muscle protein synthesis in sepsis despite unimpaired signaling to 4E-BP1 and S6K1. Am J Physiol Endocrinol Metab 281(5):E1045–E1053PubMedGoogle Scholar
  35. 35.
    Lang CH, Frost RA (2004) Differential effect of sepsis on ability of leucine and IGF-I to stimulate muscle translation initiation. Am J Physiol Endocrinol Metab 287(4):E721–E730PubMedCrossRefGoogle Scholar
  36. 36.
    Lang CH, Frost RA (2006) Glucocorticoids and TNFalpha interact cooperatively to mediate sepsis-induced leucine resistance in skeletal muscle. Mol Med 12(11–12):291–299PubMedPubMedCentralGoogle Scholar
  37. 37.
    Balage M, Averous J, Remond D, Bos C, Pujos-Guillot E, Papet I et al (2010) Presence of low-grade inflammation impaired postprandial stimulation of muscle protein synthesis in old rats. J Nutr Biochem 21(4):325–331PubMedCrossRefGoogle Scholar
  38. 38.
    Williams JP, Phillips BE, Smith K, Atherton PJ, Rankin D, Selby AL et al (2012) Effect of tumor burden and subsequent surgical resection on skeletal muscle mass and protein turnover in colorectal cancer patients. Am J Clin Nutr 96(5):1064–1070PubMedCrossRefGoogle Scholar
  39. 39.
    Deutz NE, Safar A, Schutzler S, Memelink R, Ferrando A, Spencer H et al (2011) Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food. Clin Nutr 30(6):759–768PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Winter A, Macadams J, Chevalier S (2012) Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia. Clin Nutr 31(5):765–773PubMedCrossRefGoogle Scholar
  41. 41.
    Engelen MP, Safar AM, Bartter T, Koeman F, Deutz NE (2015) High anabolic potential of essential amino acid mixtures in advanced nonsmall cell lung cancer. Ann Oncol 26(9):1960–1966PubMedCrossRefGoogle Scholar
  42. 42.
    van Dijk DP, van de Poll MC, Moses AG, Preston T, Olde Damink SW, Rensen SS et al (2015) Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients. J Cachexia Sarcopenia Muscle 6(3):212–221PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Prado CM, Sawyer MB, Ghosh S, Lieffers JR, Esfandiari N, Antoun S et al (2013) Central tenet of cancer cachexia therapy: do patients with advanced cancer have exploitable anabolic potential? Am J Clin Nutr 98(4):1012–1019PubMedCrossRefGoogle Scholar
  44. 44.
    Guillet C, Delcourt I, Rance M, Giraudet C, Walrand S, Bedu M et al (2009) Changes in basal and insulin and amino acid response of whole body and skeletal muscle proteins in obese men. J Clin Endocrinol Metab 94(8):3044–3050PubMedCrossRefGoogle Scholar
  45. 45.
    Masgrau A, Mishellany-Dutour A, Murakami H, Beaufrere AM, Walrand S, Giraudet C et al (2012) Time-course changes of muscle protein synthesis associated with obesity-induced lipotoxicity. J Physiol 590(Pt 20):5199–5210PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Hyde R, Hajduch E, Powell DJ, Taylor PM, Hundal HS (2005) Ceramide down-regulates System A amino acid transport and protein synthesis in rat skeletal muscle cells. FASEB J 19(3):461–463PubMedGoogle Scholar
  47. 47.
    Nilsson MI, Dobson JP, Greene NP, Wiggs MP, Shimkus KL, Wudeck EV et al (2013) Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J 27(10):3905–3916PubMedCrossRefGoogle Scholar
  48. 48.
    Stephens FB, Chee C, Wall BT, Murton AJ, Shannon CE, Van Loon LJ et al (2015) Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men. Diabetes 64(5):1615–1620PubMedCrossRefGoogle Scholar
  49. 49.
    Murphy J, Chevalier S, Gougeon R, Goulet ED, Morais JA (2015) Effect of obesity and type 2 diabetes on protein anabolic response to insulin in elderly women. Exp Gerontol 69:20–26PubMedCrossRefGoogle Scholar
  50. 50.
    McIntire KL, Chen Y, Sood S, Rabkin R (2014) Acute uremia suppresses leucine-induced signal transduction in skeletal muscle. Kidney Int 85(2):374–382PubMedCrossRefGoogle Scholar
  51. 51.
    Sood S, Chen Y, McIntire K, Rabkin R (2014) Acute acidosis attenuates leucine stimulated signal transduction and protein synthesis in rat skeletal muscle. Am J Nephrol 40(4):362–370PubMedCrossRefGoogle Scholar
  52. 52.
    Garibotto G, Sofia A, Russo R, Paoletti E, Bonanni A, Parodi EL et al (2015) Insulin sensitivity of muscle protein metabolism is altered in patients with chronic kidney disease and metabolic acidosis. Kidney Int 88(6):1419–1426PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Siew ED, Ikizler TA (2010) Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease. Semin Dial 23(4):378–382PubMedCrossRefGoogle Scholar
  54. 54.
    Etheridge T, Atherton PJ, Wilkinson D, Selby A, Rankin D, Webborn N et al (2011) Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise. Am J Physiol Endocrinol Metab 301(4):E697–E702PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Schakman O, Kalista S, Barbe C, Loumaye A, Thissen JP (2013) Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol 45(10):2163–2172PubMedCrossRefGoogle Scholar
  56. 56.
    Paddon-Jones D, Sheffield-Moore M, Cree MG, Hewlings SJ, Aarsland A, Wolfe RR et al (2006) Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. J Clin Endocrinol Metab 91(12):4836–4841PubMedCrossRefGoogle Scholar
  57. 57.
    Zheng X, Liang Y, He Q, Yao R, Bao W, Bao L et al (2014) Current models of mammalian target of rapamycin complex 1 [mTORC1] activation by growth factors and amino acids. Int J Mol Sci 15(11):20753–20769PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Drummond MJ, Dreyer HC, Fry CS, Glynn EL, Rasmussen BB (2009) Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. J Appl Physiol [1985] 106(4):1374–1384CrossRefGoogle Scholar
  59. 59.
    Dickinson JM, Fry CS, Drummond MJ, Gundermann DM, Walker DK, Glynn EL et al (2011) Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids. J Nutr 141(5):856–862PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Kimball SR, Jefferson LS (2010) Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise. J Biol Chem 285(38):29027–29032PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC et al (2012) A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151(6):1319–1331PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Marcotte GR, West DW, Baar K (2015) The molecular basis for load-induced skeletal muscle hypertrophy. Calcif Tissue Int 96(3):196–210PubMedCrossRefGoogle Scholar
  63. 63.
    Kelleher AR, Kimball SR, Dennis MD, Schilder RJ, Jefferson LS (2013) 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 304(2):E229–E236PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Gordon BS, Williamson DL, Lang CH, Jefferson LS, Kimball SR (2015) Nutrient-induced stimulation of protein synthesis in mouse skeletal muscle is limited by the mTORC1 repressor REDD1. J Nutr 145(4):708–713PubMedCrossRefGoogle Scholar
  65. 65.
    Guillet C, Zangarelli A, Mishellany A, Rousset P, Sornet C, Dardevet D et al (2004) Mitochondrial and sarcoplasmic proteins, but not myosin heavy chain, are sensitive to leucine supplementation in old rat skeletal muscle. Exp Gerontol 39(5):745–751PubMedCrossRefGoogle Scholar
  66. 66.
    Rivas DA, Morris EP, Haran PH, Pasha EP, Morais MS, Dolnikowski GG et al (2012) Increased ceramide content and NFkappaB signaling may contribute to the attenuation of anabolic signaling after resistance exercise in aged males. J Appl Physiol [1985] 113(11):1727–1736CrossRefGoogle Scholar
  67. 67.
    Drummond MJ, Dickinson JM, Fry CS, Walker DK, Gundermann DM, Reidy PT et al (2012) Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab 302(9):E1113–E1122PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R et al (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3(11):1014–1019PubMedCrossRefGoogle Scholar
  69. 69.
    You JS, Anderson GB, Dooley MS, Hornberger TA (2015) The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization in mice. Dis Model Mech 8(9):1059–1069PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Lang CH, Frost RA, Vary TC (2007) Regulation of muscle protein synthesis during sepsis and inflammation. Am J Physiol Endocrinol Metab 293(2):E453–E459PubMedCrossRefGoogle Scholar
  71. 71.
    Tardif N, Salles J, Guillet C, Tordjman J, Reggio S, Landrier JF et al (2014) Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2alpha activation. Aging Cell 13(6):1001–1011PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Boirie Y, Gachon P, Beaufrere B (1997) Splanchnic and whole-body leucine kinetics in young and elderly men. Am J Clin Nutr 65(2):489–495PubMedGoogle Scholar
  73. 73.
    Gorissen SH, Burd NA, Hamer HM, Gijsen AP, Groen BB, Van Loon LJ (2014) Carbohydrate coingestion delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion. J Clin Endocrinol Metab 99(6):2250–2258PubMedCrossRefGoogle Scholar
  74. 74.
    Phillips BE, Atherton PJ, Varadhan K, Limb MC, Wilkinson DJ, Sjoberg KA et al (2015) The effects of resistance exercise training on macro- and micro-circulatory responses to feeding and skeletal muscle protein anabolism in older men. J Physiol 593(12):2721–2734PubMedCrossRefGoogle Scholar
  75. 75.
    Pennings B, Groen B, de Lange A, Gijsen AP, Zorenc AH, Senden JM et al (2012) Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endocrinol Metab 302(8):E992–E999PubMedCrossRefGoogle Scholar
  76. 76.
    Yang Y, Churchward-Venne TA, Burd NA, Breen L, Tarnopolsky MA, Phillips SM (2012) Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Nutr Metab [Lond] 9(1):57PubMedCentralCrossRefGoogle Scholar
  77. 77.
    Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR et al (2012) Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr 108(10):1780–1788PubMedCrossRefGoogle Scholar
  78. 78.
    Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD (2014) Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Am J Clin Nutr 99(1):86–95PubMedCrossRefGoogle Scholar
  79. 79.
    Witard OC, Cocke TL, Ferrando AA, Wolfe RR, Tipton KD (2014) Increased net muscle protein balance in response to simultaneous and separate ingestion of carbohydrate and essential amino acids following resistance exercise. Appl Physiol Nutr Metab 39(3):329–339PubMedCrossRefGoogle Scholar
  80. 80.
    Burd NA, Gorissen SH, van Vliet S, Snijders T, Van Loon LJ (2015) Differences in postprandial protein handling after beef compared with milk ingestion during postexercise recovery: a randomized controlled trial. Am J Clin Nutr 102(4):828–836PubMedCrossRefGoogle Scholar
  81. 81.
    Koopman R, Crombach N, Gijsen AP, Walrand S, Fauquant J, Kies AK et al (2009) Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein. Am J Clin Nutr 90(1):106–115PubMedCrossRefGoogle Scholar
  82. 82.
    Walrand S, Gryson C, Salles J, Giraudet C, Migne C, Bonhomme C et al (2015) Fast-digestive protein supplement for ten days overcomes muscle anabolic resistance in healthy elderly men. Clin Nutr (in press)Google Scholar
  83. 83.
    Pennings B, Boirie Y, Senden JM, Gijsen AP, Kuipers H, Van Loon LJ (2011) Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. Am J Clin Nutr 93(5):997–1005PubMedCrossRefGoogle Scholar
  84. 84.
    Stein TP, Schluter MD, Leskiw MJ, Boden G (1999) Attenuation of the protein wasting associated with bed rest by branched-chain amino acids. Nutrition 15(9):656–660PubMedCrossRefGoogle Scholar
  85. 85.
    Paddon-Jones D, Sheffield-Moore M, Urban RJ, Sanford AP, Aarsland A, Wolfe RR et al (2004) Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab 89(9):4351–4358PubMedCrossRefGoogle Scholar
  86. 86.
    Paddon-Jones D (2006) Interplay of stress and physical inactivity on muscle loss: nutritional countermeasures. J Nutr 136(8):2123–2126PubMedGoogle Scholar
  87. 87.
    Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME et al (1994) Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330(25):1769–1775PubMedCrossRefGoogle Scholar
  88. 88.
    Ferrando AA, Paddon-Jones D, Wolfe RR (2006) Bed rest and myopathies. Curr Opin Clin Nutr Metab Care 9(4):410–415PubMedCrossRefGoogle Scholar
  89. 89.
    Verhoeven S, Vanschoonbeek K, Verdijk LB, Koopman R, Wodzig WK, Dendale P et al (2009) Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. Am J Clin Nutr 89(5):1468–1475PubMedCrossRefGoogle Scholar
  90. 90.
    Balage M, Dardevet D (2010) Long-term effects of leucine supplementation on body composition. Curr Opin Clin Nutr Metab Care 13(3):265–270PubMedCrossRefGoogle Scholar
  91. 91.
    Dardevet D, Remond D, Peyron MA, Papet I, Savary-Auzeloux I, Mosoni L (2012) Muscle wasting and resistance of muscle anabolism: the “anabolic threshold concept” for adapted nutritional strategies during sarcopenia. ScientificWorldJournal 2012:269531PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Groen BB, Res PT, Pennings B, Hertle E, Senden JM, Saris WH et al (2012) Intragastric protein administration stimulates overnight muscle protein synthesis in elderly men. Am J Physiol Endocrinol Metab 302(1):E52–E60PubMedCrossRefGoogle Scholar
  93. 93.
    Areta JL, Burke LM, Ross ML, Camera DM, West DW, Broad EM et al (2013) Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol 591(Pt 9):2319–2331PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Koopman R, Beelen M, Stellingwerff T, Pennings B, Saris WH, Kies AK et al (2007) Coingestion of carbohydrate with protein does not further augment postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab 293(3):E833–E842PubMedCrossRefGoogle Scholar
  95. 95.
    Weijs PJ, Cynober L, Delegge M, Kreymann G, Wernerman J, Wolfe RR (2014) Proteins and amino acids are fundamental to optimal nutrition support in critically ill patients. Crit Care 18(6):591PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Ferrando AA, Paddon-Jones D, Wolfe RR (2002) Alterations in protein metabolism during space flight and inactivity. Nutrition 18(10):837–841PubMedCrossRefGoogle Scholar
  97. 97.
    Devries MC, Phillips SM (2015) Supplemental protein in support of muscle mass and health: advantage whey. J Food Sci 80(Suppl 1):A8–A15PubMedCrossRefGoogle Scholar
  98. 98.
    Hagerman FC, Walsh SJ, Staron RS, Hikida RS, Gilders RM, Murray TF et al (2000) Effects of high-intensity resistance training on untrained older men. I. Strength, cardiovascular, and metabolic responses. J Gerontol A Biol Sci Med Sci 55(7):B336–B346PubMedCrossRefGoogle Scholar
  99. 99.
    Little JP, Phillips SM (2009) Resistance exercise and nutrition to counteract muscle wasting. Appl Physiol Nutr Metab 34(5):817–828PubMedCrossRefGoogle Scholar
  100. 100.
    Costamagna D, Costelli P, Sampaolesi M, Penna F (2015) Role of inflammation in muscle homeostasis and myogenesis. Mediators Inflamm 2015:805172PubMedPubMedCentralGoogle Scholar
  101. 101.
    Rieu I, Magne H, Savary-Auzeloux I, Averous J, Bos C, Peyron MA et al (2009) Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats. J Physiol 587(Pt 22):5483–5492PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Trappe TA, Carroll CC, Dickinson JM, LeMoine JK, Haus JM, Sullivan BE et al (2011) Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. Am J Physiol Regul Integr Comp Physiol 300(3):R655–R662PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ et al (2011) Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 93(2):402–412PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Pôle Endocrinologie, Diabétologie et NutritionInstitut de Recherches Expérimentales et Cliniques, Université Catholique de LouvainBruxellesBelgium

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