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Erschienen in: European Journal of Applied Physiology 4/2014

01.04.2014 | Original Article

Whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in human skeletal muscle

verfasst von: Ryo Kakigi, Toshinori Yoshihara, Hayao Ozaki, Yuji Ogura, Noriko Ichinoseki-Sekine, Hiroyuki Kobayashi, Hisashi Naito

Erschienen in: European Journal of Applied Physiology | Ausgabe 4/2014

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Abstract

Purpose

Protein ingestion after resistance exercise increases muscle protein synthesis (MPS) in a dose-dependent manner. However, the molecular mechanism(s) for the dose-dependency of MPS remains unclear. This study aimed to determine the dose response of mammalian target of rapamycin (mTOR) signaling in muscle with ingestion of protein after resistance exercise.

Methods

Fifteen male subjects performed four sets of six unilateral isokinetic concentric knee extensions. Immediately after exercise, eight subjects consumed water only. The other seven subjects, in a randomized-order crossover design, took either a 10 [3.6 g essential amino acids (EAA)] or 20 g (7.1 g EAA) solution of whey protein. Muscle biopsies from the vastus lateralis muscle were taken 30 min before and 1 h after resistance exercise. Phosphorylation of Akt (Ser473), mTOR (Ser2448), 4E-BP1 (Thr37/46), and S6K1 (Thr389) was measured by western blotting.

Results

Concentric knee extension exercise alone did not increase phosphorylation of Akt and mTOR 1 h after exercise, but ingesting protein after exercise significantly increased the phosphorylation of Akt and mTOR in a dose-dependent manner (P < 0.05). 4E-BP1 phosphorylation significantly decreased after resistance exercise (P < 0.05), but subjects who took 10 or 20 g of protein after exercise showed increased 4E-BP1 from post-exercise dephosphorylation (P < 0.05). S6K1 phosphorylation significantly increased after resistance exercise (P < 0.05), and 20 g of protein further increased S6K1 phosphorylation compared with ingestion of 10 g (P < 0.05).

Conclusions

These findings suggest that whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in untrained men.
Literatur
Zurück zum Zitat Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D, Smith K, Rennie MJ (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):1080–1088. doi:10.3945/ajcn.2010.29819 PubMedCrossRef Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D, Smith K, Rennie MJ (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):1080–1088. doi:10.​3945/​ajcn.​2010.​29819 PubMedCrossRef
Zurück zum Zitat Biolo G, Maggi SP, Williams BD, Tipton KD, Wolfe RR (1995) Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Am J Physiol 268(3 Pt 1):E514–E520PubMed Biolo G, Maggi SP, Williams BD, Tipton KD, Wolfe RR (1995) Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Am J Physiol 268(3 Pt 1):E514–E520PubMed
Zurück zum Zitat 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 273(1 Pt 1):E122–E129PubMed 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 273(1 Pt 1):E122–E129PubMed
Zurück zum Zitat Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrere B (1997) Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA 94(26):14930–14935PubMedCentralPubMedCrossRef Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrere B (1997) Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA 94(26):14930–14935PubMedCentralPubMedCrossRef
Zurück zum Zitat Bolster DR, Jefferson LS, Kimball SR (2004) Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling. Proc Nutr Soc 63(2):351–356. doi:10.1079/PNS2004355 PubMedCrossRef Bolster DR, Jefferson LS, Kimball SR (2004) Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling. Proc Nutr Soc 63(2):351–356. doi:10.​1079/​PNS2004355 PubMedCrossRef
Zurück zum Zitat Burd NA, Holwerda AM, Selby KC, West DW, Staples AW, Cain NE, Cashaback JG, Potvin JR, Baker SK, Phillips SM (2010a) Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men. J Physiol 588(Pt 16):3119–3130. doi:10.1113/jphysiol.2010.192856 PubMedCentralPubMedCrossRef Burd NA, Holwerda AM, Selby KC, West DW, Staples AW, Cain NE, Cashaback JG, Potvin JR, Baker SK, Phillips SM (2010a) Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men. J Physiol 588(Pt 16):3119–3130. doi:10.​1113/​jphysiol.​2010.​192856 PubMedCentralPubMedCrossRef
Zurück zum Zitat Burd NA, West DW, Staples AW, Atherton PJ, Baker JM, Moore DR, Holwerda AM, Parise G, Rennie MJ, Baker SK, Phillips SM (2010b) Low-load high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in young men. PLoS One 5(8):e12033. doi:10.1371/journal.pone.0012033 PubMedCentralPubMedCrossRef Burd NA, West DW, Staples AW, Atherton PJ, Baker JM, Moore DR, Holwerda AM, Parise G, Rennie MJ, Baker SK, Phillips SM (2010b) Low-load high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in young men. PLoS One 5(8):e12033. doi:10.​1371/​journal.​pone.​0012033 PubMedCentralPubMedCrossRef
Zurück zum Zitat Coffey VG, Zhong Z, Shield A, Canny BJ, Chibalin AV, Zierath JR, Hawley JA (2006) Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. Faseb J 20(1):190–192. doi:10.1096/fj.05-4809fje PubMed Coffey VG, Zhong Z, Shield A, Canny BJ, Chibalin AV, Zierath JR, Hawley JA (2006) Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. Faseb J 20(1):190–192. doi:10.​1096/​fj.​05-4809fje PubMed
Zurück zum Zitat Dangin M, Boirie Y, Garcia-Rodenas C, Gachon P, Fauquant J, Callier P, Ballevre O, Beaufrere B (2001) The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol Endocrinol Metab 280(2):E340–E348PubMed Dangin M, Boirie Y, Garcia-Rodenas C, Gachon P, Fauquant J, Callier P, Ballevre O, Beaufrere B (2001) The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol Endocrinol Metab 280(2):E340–E348PubMed
Zurück zum Zitat Dickinson JM, Fry CS, Drummond MJ, Gundermann DM, Walker DK, Glynn EL, Timmerman KL, Dhanani S, Volpi E, Rasmussen BB (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):856–862. doi:10.3945/jn.111.139485 PubMedCentralPubMedCrossRef Dickinson JM, Fry CS, Drummond MJ, Gundermann DM, Walker DK, Glynn EL, Timmerman KL, Dhanani S, Volpi E, Rasmussen BB (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):856–862. doi:10.​3945/​jn.​111.​139485 PubMedCentralPubMedCrossRef
Zurück zum Zitat Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB (2008) Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab 294(2):E392–E400. doi:10.1152/ajpendo.00582.2007 PubMedCentralPubMedCrossRef Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB (2008) Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab 294(2):E392–E400. doi:10.​1152/​ajpendo.​00582.​2007 PubMedCentralPubMedCrossRef
Zurück zum Zitat Eliasson J, Elfegoun T, Nilsson J, Kohnke R, Ekblom B, Blomstrand E (2006) Maximal lengthening contractions increase p70 S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. Am J Physiol Endocrinol Metab 291(6):E1197–E1205. doi:10.1152/ajpendo.00141.2006 PubMedCrossRef Eliasson J, Elfegoun T, Nilsson J, Kohnke R, Ekblom B, Blomstrand E (2006) Maximal lengthening contractions increase p70 S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. Am J Physiol Endocrinol Metab 291(6):E1197–E1205. doi:10.​1152/​ajpendo.​00141.​2006 PubMedCrossRef
Zurück zum Zitat Glynn EL, Fry CS, Drummond MJ, Dreyer HC, Dhanani S, Volpi E, Rasmussen BB (2010a) 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–R540. doi:10.1152/ajpregu.00077.2010 PubMedCentralPubMedCrossRef Glynn EL, Fry CS, Drummond MJ, Dreyer HC, Dhanani S, Volpi E, Rasmussen BB (2010a) 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–R540. doi:10.​1152/​ajpregu.​00077.​2010 PubMedCentralPubMedCrossRef
Zurück zum Zitat Ha E, Zemel MB (2003) Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review). J Nutr Biochem 14(5):251–258PubMedCrossRef Ha E, Zemel MB (2003) Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review). J Nutr Biochem 14(5):251–258PubMedCrossRef
Zurück zum Zitat Hulmi JJ, Kovanen V, Selanne H, Kraemer WJ, Hakkinen K, Mero AA (2009) Acute and long-term effects of resistance exercise with or without protein ingestion on muscle hypertrophy and gene expression. Amino Acids 37(2):297–308. doi:10.1007/s00726-008-0150-6 PubMedCrossRef Hulmi JJ, Kovanen V, Selanne H, Kraemer WJ, Hakkinen K, Mero AA (2009) Acute and long-term effects of resistance exercise with or without protein ingestion on muscle hypertrophy and gene expression. Amino Acids 37(2):297–308. doi:10.​1007/​s00726-008-0150-6 PubMedCrossRef
Zurück zum Zitat Kakigi R, Naito H, Ogura Y, Kobayashi H, Saga N, Ichinoseki-Sekine N, Yoshihara T, Katamoto S (2011) Heat stress enhances mTOR signaling after resistance exercise in human skeletal muscle. J Physiol Sci 61(2):131–140. doi:10.1007/s12576-010-0130-y PubMedCrossRef Kakigi R, Naito H, Ogura Y, Kobayashi H, Saga N, Ichinoseki-Sekine N, Yoshihara T, Katamoto S (2011) Heat stress enhances mTOR signaling after resistance exercise in human skeletal muscle. J Physiol Sci 61(2):131–140. doi:10.​1007/​s12576-010-0130-y PubMedCrossRef
Zurück zum Zitat Koopman R, Zorenc AH, Gransier RJ, Cameron-Smith D, van Loon LJ (2006) Increase in S6K1 phosphorylation in human skeletal muscle following resistance exercise occurs mainly in type II muscle fibers. Am J Physiol Endocrinol Metab 290(6):E1245–E1252. doi:10.1152/ajpendo.00530.2005 PubMedCrossRef Koopman R, Zorenc AH, Gransier RJ, Cameron-Smith D, van Loon LJ (2006) Increase in S6K1 phosphorylation in human skeletal muscle following resistance exercise occurs mainly in type II muscle fibers. Am J Physiol Endocrinol Metab 290(6):E1245–E1252. doi:10.​1152/​ajpendo.​00530.​2005 PubMedCrossRef
Zurück zum Zitat Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O, Hiscock N, Rennie MJ (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):211–217. doi:10.1113/jphysiol.2008.164483 PubMedCentralPubMedCrossRef Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O, Hiscock N, Rennie MJ (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):211–217. doi:10.​1113/​jphysiol.​2008.​164483 PubMedCentralPubMedCrossRef
Zurück zum Zitat Mascher H, Tannerstedt J, Brink-Elfegoun T, Ekblom B, Gustafsson T, Blomstrand E (2008) Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle. Am J Physiol Endocrinol Metab 294(1):E43–E51. doi:10.1152/ajpendo.00504.2007 PubMedCrossRef Mascher H, Tannerstedt J, Brink-Elfegoun T, Ekblom B, Gustafsson T, Blomstrand E (2008) Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle. Am J Physiol Endocrinol Metab 294(1):E43–E51. doi:10.​1152/​ajpendo.​00504.​2007 PubMedCrossRef
Zurück zum Zitat Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM (2009) Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr 89(1):161–168. doi:10.3945/ajcn.2008.26401 PubMedCrossRef Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM (2009) Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr 89(1):161–168. doi:10.​3945/​ajcn.​2008.​26401 PubMedCrossRef
Zurück zum Zitat Nader GA, Esser KA (2001) Intracellular signaling specificity in skeletal muscle in response to different modes of exercise. J Appl Physiol 90(5):1936–1942PubMed Nader GA, Esser KA (2001) Intracellular signaling specificity in skeletal muscle in response to different modes of exercise. J Appl Physiol 90(5):1936–1942PubMed
Zurück zum Zitat Nair KS, Schwartz RG, Welle S (1992) Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. Am J Physiol 263(5 Pt 1):E928–E934PubMed Nair KS, Schwartz RG, Welle S (1992) Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. Am J Physiol 263(5 Pt 1):E928–E934PubMed
Zurück zum Zitat 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):997–1005. doi:10.3945/ajcn.110.008102 PubMedCrossRef 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):997–1005. doi:10.​3945/​ajcn.​110.​008102 PubMedCrossRef
Zurück zum Zitat 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–E107PubMed 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–E107PubMed
Zurück zum Zitat Reitelseder S, Agergaard J, Doessing S, Helmark IC, Lund P, Kristensen NB, Frystyk J, Flyvbjerg A, Schjerling P, van Hall G, Kjaer M, Holm L (2011) Whey and casein labeled with L-[1-13C] leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion. Am J Physiol Endocrinol Metab 300(1):E231–E242. doi:10.1152/ajpendo.00513.2010 PubMedCrossRef Reitelseder S, Agergaard J, Doessing S, Helmark IC, Lund P, Kristensen NB, Frystyk J, Flyvbjerg A, Schjerling P, van Hall G, Kjaer M, Holm L (2011) Whey and casein labeled with L-[1-13C] leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion. Am J Physiol Endocrinol Metab 300(1):E231–E242. doi:10.​1152/​ajpendo.​00513.​2010 PubMedCrossRef
Zurück zum Zitat Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM (2009) Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol 107(3):987–992. doi:10.1152/japplphysiol.00076.2009 PubMedCrossRef Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM (2009) Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol 107(3):987–992. doi:10.​1152/​japplphysiol.​00076.​2009 PubMedCrossRef
Zurück zum Zitat Wilkinson SB, Phillips SM, Atherton PJ, Patel R, Yarasheski KE, Tarnopolsky MA, Rennie MJ (2008) Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle. J Physiol 586(Pt 15):3701–3717. doi:10.1113/jphysiol.2008.153916 PubMedCentralPubMedCrossRef Wilkinson SB, Phillips SM, Atherton PJ, Patel R, Yarasheski KE, Tarnopolsky MA, Rennie MJ (2008) Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle. J Physiol 586(Pt 15):3701–3717. doi:10.​1113/​jphysiol.​2008.​153916 PubMedCentralPubMedCrossRef
Zurück zum Zitat Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA, Phillips SM (2012) Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr 108(10):1780–1788. doi:10.1017/S0007114511007422 PubMedCrossRef Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA, Phillips SM (2012) Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr 108(10):1780–1788. doi:10.​1017/​S000711451100742​2 PubMedCrossRef
Metadaten
Titel
Whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in human skeletal muscle
verfasst von
Ryo Kakigi
Toshinori Yoshihara
Hayao Ozaki
Yuji Ogura
Noriko Ichinoseki-Sekine
Hiroyuki Kobayashi
Hisashi Naito
Publikationsdatum
01.04.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Applied Physiology / Ausgabe 4/2014
Print ISSN: 1439-6319
Elektronische ISSN: 1439-6327
DOI
https://doi.org/10.1007/s00421-013-2812-7

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