Skeletal muscle hypertrophy adaptations predominate in the early stages of resistance exercise training, matching deuterium oxide-derived measures of muscle protein synthesis and mechanistic target of rapamycin complex 1 signaling

FASEB Journal

Volumn 29, Issue 11, 2015, Pages 4485-4496

  Brook, Matthew S ^a   Wilkinson, Daniel J ^a   Mitchell, William K ^a,b   Lund, Jonathan N ^a,b   Szewczyk, Nathaniel J ^a   Greenhaff, Paul L ^a   Smith, Ken ^a   Atherton, Philip J ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b ROYAL DERBY HOSPITAL   (United Kingdom)

Author keywords

Anabolic signaling; D20; Stable isotopes

Indexed keywords

DEUTERIUM OXIDE; ISOTOPE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MUSCLE PROTEIN;

ADULT; ARTICLE; ATOM; BODY WATER; BONE MASS; CLINICAL ARTICLE; CONTROLLED STUDY; GAS CHROMATOGRAPHY; HIGH TEMPERATURE; HUMAN; HUMAN TISSUE; LEG; MALE; MASS SPECTROMETRY; MUSCLE BIOPSY; MUSCLE HYPERTROPHY; MUSCLE MASS; PRIORITY JOURNAL; PROTEIN SYNTHESIS; PYROLYSIS; RESISTANCE TRAINING; THICKNESS; ADAPTATION; BIOSYNTHESIS; CLINICAL TRIAL; EXERCISE; HYPERTROPHY; METABOLISM; PHYSIOLOGY; SKELETAL MUSCLE;

ADAPTATION, PHYSIOLOGICAL; ADULT; DEUTERIUM OXIDE; EXERCISE; HUMANS; HYPERTROPHY; MALE; MUSCLE PROTEINS; MUSCLE, SKELETAL;

EID: 84948798847     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.15-273755     Document Type: Article

References (70)

1. Goldberg, A. L., Etlinger, J. D., Goldspink, D. F., and Jablecki, C. (1975)Mechanismof work-induced hypertrophy of skeletalmuscle. Med. Sci. Sports 7, 185-198.
2. Warburton, D. E. R., Nicol, C.W., and Bredin, S. S.D. (2006)Health benefits of physical activity: The evidence. CMAJ 174, 801-809.
3. Laurent, G. J., and Sparrow, M. P. (1977)Changes in RNA, DNAand protein content and the rates of protein synthesis and degradation during hypertrophy of the anterior latissimus dorsi muscle of the adult fowl (Gallus domesticus). Growth 41, 249-262.
4. Burd, N. A., West, D. W. D., Moore, D. R., Atherton, P. J., Staples, A. W., Prior, T., Tang, J. E., Rennie, M. J., Baker, S. K., and Phillips, S.M. (2011) Enhanced amino acid sensitivity ofmyofibrillar protein synthesis persists for up to 24 h after resistance exercise in young men. J. Nutr. 141, 568-573.
5. Witard, O. C., Jackman, S. R., Breen, L., Smith, K., Selby, A., and Tipton, K. D. (2014) Myofibrillar muscle protein synthesis rates subsequent to ameal inresponse toincreasingdoses ofwhey protein at rest and after resistance exercise. Am. J. Clin. Nutr. 99, 86-95.
6. Phillips, B. E., Hill, D. S., and Atherton, P. J. (2012) Regulation of muscle protein synthesis in humans. Curr. Opin. Clin. Nutr. Metab. Care 15, 58-63.
7. Moritani, T., and deVries, H. A. (1979) Neural factors versus hypertrophy in the time course ofmuscle strength gain. Am. J. Phys. Med. 58, 115-130.
8. Häkkinen, K., Newton, R. U., Gordon, S. E., McCormick, M., Volek, J. S., Nindl, B. C., Gotshalk, L. A., Campbell, W. W., Evans, W. J., Häkkinen, A., Humphries, B. J., and Kraemer, W. J. (1998) Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men. J. Gerontol. A Biol. Sci. Med. Sci. 53, B415-B423.
9. Staron, R. S., Karapondo, D. L., Kraemer, W. J., Fry, A. C., Gordon, S. E., Falkel, J. E., Hagerman, F. C., and Hikida, R. S. (1994) Skeletal muscle adaptations during early phase of heavy-resistance training in men and women. J. Appl. Physiol. 76, 1247-1255.
10. Abe, T., DeHoyos, D. V., Pollock, M. L., and Garzarella, L. (2000) Time course for strength and muscle thickness changes following upper and lower body resistance training inmen and women. Eur. J. Appl. Physiol. 81, 174-180.
11. Seynnes, O. R., de Boer, M., andNarici, M. V. (2007) Early skeletal muscle hypertrophy and architectural changes in response to highintensity resistance training. J. Appl. Physiol. 102, 368-373.
12. DeFreitas, J.M., Beck, T.W., Stock, M. S., Dillon, M. A., and Kasishke II, P. R. (2011) An examination of the time course of traininginduced skeletal muscle hypertrophy. Eur. J. Appl. Physiol. 111, 2785-2790.
13. Woolstenhulme, M.T., Conlee, R.K., Drummond, M. J., Stites, A. W., and Parcell, A. C. (2006) Temporal response of desmin and dystrophin proteins to progressive resistance exercise in human skeletal muscle. J. Appl. Physiol. 100, 1876-1882.
14. Baroni, B.M., Geremia, J. M., Rodrigues, R., De AzevedoFranke, R., Karamanidis, K., and Vaz, M. A. (2013) Muscle architecture adaptations to knee extensor eccentric training: rectus femoris vs. vastus lateralis. Muscle Nerve 48, 498-506.
15. Ogasawara, R., Yasuda, T., Ishii, N., and Abe, T. (2013) Comparison of muscle hypertrophy following 6-month of continuous and periodic strength training. Eur. J. Appl. Physiol. 113, 975-985.
16. Alway, S. E., Grumbt, W. H., Stray-Gundersen, J., and Gonyea, W. J. (1992) Effects of resistance training on elbow flexors of highly competitive bodybuilders. J. Appl. Physiol. 72, 1512-1521.
17. Ahtiainen, J. P., Pakarinen, A., Alen, M., Kraemer, W. J., and Häkkinen, K. (2003)Muscle hypertrophy, hormonal adaptations and strength development during strength training in strength-trained and untrained men. Eur. J. Appl. Physiol. 89, 555-563.
18. Heymsfield, S. B., Wang, Z., Baumgartner, R.N., and Ross, R. (1997) Human body composition: Advances inmodels andmethods. Annu. Rev. Nutr. 17, 527-558.
19. Bemben, M. G. (2002) Use of diagnostic ultrasound for assessing muscle size. J. Strength Cond. Res. 16, 103-108.
20. Reeves, N. D., Maganaris, C. N., and Narici, M. V. (2004) Ultrasonographic assessment of human skeletal muscle size. Eur. J. Appl. Physiol. 91, 116-118.
21. Abe, T., Kawakami, Y., Suzuki, Y., Gunji, A., and Fukunaga, T. (1997) Effects of 20 days bed rest onmusclemorphology. J. Gravit. Physiol. 4, S10-S14.
22. Esformes, J. I., Narici, M. V., and Maganaris, C. N. (2002) Measurement of human muscle volume using ultrasonography. Eur. J. Appl. Physiol. 87, 90-92.
23. Aagaard, P., Andersen, J. L., Dyhre-Poulsen, P., Leffers, A. M., Wagner, A., Magnusson, S. P., Halkjaer-Kristensen, J., and Simonsen, E. B. (2001) A mechanism for increased contractile strength of human pennatemuscle in response to strength training: changes in muscle architecture. J. Physiol. 534, 613-623.
24. Franchi, M. V., Atherton, P. J., Reeves, N. D., Flück, M., Williams, J., Mitchell, W. K., Selby, A., Beltran Valls, R. M., and Narici, M. V. (2014) Architectural, functional and molecular responses to concentric and eccentric loading in human skeletal muscle. Acta Physiol. (Oxf.) 210, 642-654.
25. Drummond, M. J., Fry, C. S., Glynn, E. L., Dreyer, H. C., Dhanani, S., Timmerman, K. L., Volpi, E., and Rasmussen, B. B. (2009) Rapamycin administration in humans blocks the contractioninduced increase in skeletal muscle protein synthesis. J. Physiol. 587, 1535-1546.
26. Murton, A. J., Billeter, R., Stephens, F. B., Des Etages, S.G., Graber, F., Hill, R. J., Marimuthu, K., and Greenhaff, P. L. (2014) Transient transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training. J. Appl. Physiol. 116, 113-125.
27. Fry, C. S., Drummond, M. J., Glynn, E. L., Dickinson, J. M., Gundermann, D.M., Timmerman, K. L., Walker, D.K., Dhanani, S., Volpi, E., and Rasmussen, B. B. (2011) Aging impairs contractioninduced human skeletal muscle mTORC1 signaling and protein synthesis. Skelet. Muscle 1, 11.
28. Kumar, V., Selby, A., Rankin, D., Patel, R., Atherton, P., Hildebrandt, W., Williams, J., Smith, K., Seynnes, O., Hiscock, N., and Rennie, M. J. (2009) Age-related differences in the dose-response relationship of muscleproteinsynthesis to resistance exercise inyoung andoldmen. J. Physiol. 587, 211-217.
29. Mitchell, C. J., Churchward-Venne, T. A., Parise, G., Bellamy, L., Baker, S. K., Smith, K., Atherton, P. J., and Phillips, S.M. (2014) Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-inducedmuscle hypertrophy in youngmen. PLoS One 9, e89431.
30. Mayhew, D. L., Kim, J. S., Cross, J.M., Ferrando, A. A., and Bamman, M.M. (2009) Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans. J. Appl. Physiol. 107, 1655-1662.
31. Gasier, H.G., Fluckey, J. D., Previs, S.F., Wiggs, M.P., andRiechman, S. E. (2012) Acute resistance exercise augments integrative myofibrillar protein synthesis. Metabolism 61, 153-156.
32. Robinson, M.M., Turner, S.M., Hellerstein, M. K., Hamilton, K. L., andMiller, B. F. (2011) Long-termsynthesis rates of skeletalmuscle DNA and protein are higher during aerobic training in older humans than in sedentary young subjects but are not altered by protein supplementation. FASEB J. 25, 3240-3249.
33. Busch, R., Kim, Y. K., Neese, R. A., Schade-Serin, V., Collins, M., Awada, M., Gardner, J.L., Beysen, C., Marino, M.E., Misell, L.M., and Hellerstein, M. K. (2006)Measurement of protein turnover rates by heavy water labeling of nonessential amino acids. Biochim. Biophys. Acta 1760, 730-744.
34. Wilkinson, D. J., Franchi, M. V., Brook, M. S., Narici, M. V., Williams, J. P., Mitchell, W. K., Szewczyk, N. J., Greenhaff, P. L., Atherton, P. J., and Smith, K. (2014) A validation of the application of D(2)O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans. Am. J. Physiol. Endocrinol. Metab. 306, E571-E579.
35. Dietrichson, P., Coakley, J., Smith, P. E., Griffiths, R. D., Helliwell, T. R., and Edwards, R. H. (1987) Conchotome and needle percutaneous biopsy of skeletal muscle. J. Neurol. Neurosurg. Psychiatry 50, 1461-1467.
36. MacDonald, A. J., Small, A. C., Greig, C. A., Husi, H., Ross, J. A., Stephens, N. A., Fearon, K. C.H., andPreston, T. (2013)Anovel oral tracer procedure for measurement of habitual myofibrillar protein synthesis. Rapid Commun. Mass Spectrom. 27, 1769-1777.
37. Crossland, H., Kazi, A. A., Lang, C. H., Timmons, J. A., Pierre, P., Wilkinson, D. J., Smith, K., Szewczyk, N. J., and Atherton, P. J. (2013) Focal adhesion kinase is required for IGF-I-mediated growth of skeletal muscle cells via a TSC2/mTOR/S6K1-associated pathway. Am. J. Physiol. Endocrinol.Metab. 305, E183-E193.
38. Welinder, C., and Ekblad, L. (2011) Coomassie staining as loading control in Western blot analysis. J. Proteome Res. 10, 1416-1419.
39. Heymsfield, S.B., Adamek, M., Gonzalez, M. C., Jia, G., and Thomas, D.M. (2014) Assessing skeletalmusclemass: historical overview and state of the art. J. Cachexia Sarcopenia Muscle 5, 9-18.
40. Thomaes, T., Thomis, M., Onkelinx, S., Coudyzer, W., Cornelissen, V., and Vanhees, L. (2012) Reliability and validity of the ultrasound technique to measure the rectus femoris muscle diameter in older CAD-patients. BMC Med. Imaging 12, 7.
41. Giles, L. S., Webster, K.E., McClelland, J.A., and Cook, J. (2015)Can ultrasound measurements of muscle thickness be used to measure the size of individual quadriceps muscles in people with patellofemoral pain? Phys. Ther. Sport 16, 45-52.
42. Miyatani, M., Kanehisa, H., Kuno, S., Nishijima, T., and Fukunaga, T. (2002) Validity of ultrasonograph muscle thickness measurements for estimating muscle volume of knee extensors in humans. Eur. J. Appl. Physiol. 86, 203-208.
43. Miyatani, M., Kanehisa, H., Ito, M., Kawakami, Y., and Fukunaga, T. (2004) The accuracy of volume estimates using ultrasound muscle thickness measurements in different muscle groups. Eur. J. Appl. Physiol. 91, 264-272.
44. Wernbom, M., Augustsson, J., and Thomée, R. (2007) The influence of frequency, intensity, volume and mode of strength training on whole muscle cross-sectional area in humans. Sports Med. 37, 225-264.
45. Rabita, G., Pérot, C., andLensel-Corbeil, G. (2000)Differential effect of knee extension isometric training on the differentmuscles of the quadriceps femoris in humans. Eur. J. Appl. Physiol. 83, 531-538.
46. Tesch, P.A., Ekberg, A., Lindquist, D. M., and Trieschmann, J. T.(2004) Muscle hypertrophy following 5-week resistance training using a nongravity- dependent exercise system. Acta Physiol. Scand. 180, 89-98.
47. Constantin, D., McCullough, J., Mahajan, R. P., and Greenhaff, P. L. (2011) Novel events in the molecular regulation of muscle mass in critically ill patients. J. Physiol. 589, 3883-3895.
48. Phillips, B. E., Williams, J. P., Gustafsson, T., Bouchard, C., Rankinen, T., Knudsen, S., Smith, K., Timmons, J. A., and Atherton, P. J. (2013) Molecular networks of human muscle adaptation to exercise and age. PLoS Genet. 9, e1003389.
49. Smith, G. I., Patterson, B. W., and Mittendorfer, B. (2011) Human muscle protein turnover-why is it so variable? J. Appl. Physiol. 110, 480-491.
50. Kumar, V., Atherton, P., Smith, K., and Rennie, M. J. (2009)Human muscle protein synthesis and breakdown during and after exercise. J. Appl. Physiol. 106, 2026-2039.
51. Cuthbertson, D., Smith, K., Babraj, J., Leese, G., Waddell, T., Atherton, P., Wackerhage, H., Taylor, P.M., and Rennie, M. J. (2005) Anabolic signaling deficits underlie amino acid resistance ofwasting, aging muscle. FASEB J. 19, 422-424.
52. Kasumov, T., Ilchenko, S., Li, L., Rachdaoui, N., Sadygov, R. G., Willard, B., McCullough, A. J., and Previs, S. (2011) Measuring protein synthesis using metabolic 2H labeling, high-resolution mass spectrometry, and an algorithm. Anal. Biochem. 412, 47-55.
53. Kasumov, T., Dabkowski, E. R., Shekar, K. C., Li, L., Ribeiro Jr., R. F., Walsh, K., Previs, S. F., Sadygov, R. G., Willard, B., and Stanley, W. C. (2013) Assessment of cardiac proteome dynamics with heavy water: slower protein synthesis rates in interfibrillar than subsarcolemmal mitochondria. Am. J. Physiol. Heart Circ. Physiol. 304, H1201-H1214.
54. Kumar, V., Atherton, P. J., Selby, A., Rankin, D., Williams, J., Smith, K., Hiscock, N., and Rennie, M. J. (2012) Muscle protein synthetic responses to exercise: effects of age, volume, and intensity. J. Gerontol. A Biol. Sci. Med. Sci. 67, 1170-1177.
55. Miller, B. F., Olesen, J. L., Hansen, M., Døssing, S., Crameri, R. M., Welling, R. J., Langberg, H., Flyvbjerg, A., Kjaer, M., Babraj, J. A., Smith, K., and Rennie, M. J. (2005) Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise. J. Physiol. 567, 1021-1033.
56. Phillips, S.M., Tipton, K.D., Ferrando, A. A., andWolfe, R. R. (1999) Resistance training reduces the acute exercise-induced increase in muscle protein turnover. Am. J. Physiol. 276, E118-E124.
57. Tang, J. E., Perco, J. G., Moore, D. R., Wilkinson, S. B., and Phillips, S.M. (2008)Resistance training alters the responseof fedstatemixed muscle protein synthesis in young men. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R172-R178.
58. Kim, P.L., Staron, R. S., andPhillips, S.M. (2005)Fasted-state skeletal muscle protein synthesis after resistance exercise is altered with training. J. Physiol. 568, 283-290.
59. Wilkinson, S. B., Tarnopolsky, M. A., Grant, E. J., Correia, C. E., and Phillips, S.M. (2006)Hypertrophy with unilateral resistance exercise occurs without increases in endogenous anabolic hormone concentration. Eur. J. Appl. Physiol. 98, 546-555.
60. Cheek, D. B. (1968) Human Growth: Body Composition, Cell Growth, Energy, and Intelligence, Lea & Febiger, Philadelphia.
61. Goldberg, A. L. (1967) Protein synthesis in tonic and phasic skeletal muscles. Nature 216, 1219-1220.
62. Forsberg, A. M., Nilsson, E., Werneman, J., Bergström, J., and Hultman, E. (1991) Muscle composition in relation to age and sex. Clin. Sci. 81, 249-256.
63. Chesley, A., MacDougall, J. D., Tarnopolsky, M. A., Atkinson, S. A., and Smith, K. (1992) Changes in human muscle protein synthesis after resistance exercise. J. Appl. Physiol. 73, 1383-1388.
64. Bickel, C. S., Slade, J., Mahoney, E., Haddad, F., Dudley, G. A., and Adams, G. R. (2005) Time course ofmolecular responses of human skeletal muscle to acute bouts of resistance exercise. J. Appl. Physiol. 98, 482-488.
65. Haddad, F., Baldwin, K.M., and Tesch, P.A. (2005) Pretranslational markers of contractile protein expression in human skeletalmuscle: effect of limb unloading plus resistance exercise. J. Appl. Physiol. 98, 46-52.
66. Drummond, M. J., Dreyer, H. C., Fry, C. S., Glynn, E. L., and Rasmussen, B. B. (2009) Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. J. Appl. Physiol. 106, 1374-1384.
67. Dreyer, H. C., Fujita, S., Cadenas, J. G., Chinkes, D. L., Volpi, E., and Rasmussen, B. B. (2006) Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J. Physiol. 576, 613-624.
68. Nader, G.A., vonWalden, F., Liu, C., Lindvall, J., Gutmann, L., Pistilli, E. E., and Gordon, P. M. (2014) Resistance exercise training modulates acute gene expression during human skeletal muscle hypertrophy. J. Appl. Physiol. 116, 693-702.
69. Gonzalez, A. M., Hoffman, J. R., Townsend, J. R., Jajtner, A. R., Wells, A. J., Beyer, K. S., Willoughby, D. S., Oliveira, L. P., Fukuda, D.H., Fragala, M. S., and Stout, J. R. (2015)Association between myosin heavy chain protein isoforms and intramuscular anabolic signaling following resistance exercise in trained men. Physiol. Rep. 3, e12268.
70. Wilkinson, S. B., Phillips, S. M., Atherton, P. J., Patel, R., Yarasheski, K. E., Tarnopolsky, M. A., and Rennie, M. J. (2008) Differential effects of resistance and endurance exercise in the fed state on signallingmolecule phosphorylation and protein synthesis inhuman muscle. J. Physiol. 586, 3701-3717.