Background: Although the effect of whey protein intake on protein metabolism in exercise-loaded skeletal muscle has been well documented, little has been reported on its effect on resting muscle. The effects of whey protein intake on protein metabolism in resting mouse skeletal muscle were investigated. Methods: Mice were fed AIN-93G composed of either casein or whey protein as the protein source for 3 or 7 consecutive days. The gastrocnemius muscle was excised, and the expression levels of the regulatory factor, mTOR, and its subunits, Raptor and Rictor, were measured by real-time PCR. The protein expression levels of mTOR and its phosphorylated form were measured by immunofluorescent western blotting. The effects of whey protein were compared to those of the case in control. Results: mTOR expression increased in the gastrocnemius muscle of mice fed whey protein for 7 consecutive days. The expression of Raptor significantly increased, whereas that of Rictor did not change, suggesting a dominant formation of mTORC1 relating to the upregulation of protein synthesis. The protein levels of mTOR and its phosphorylated form significantly increased in mice fed whey protein, indicating enhanced protein synthesis. Increased mTOR expression was not seen in the gastrocnemius muscle of mice fed whey protein for 3 consecutive days. Conclusions: These results indicate that the intake of whey protein for 7 consecutive days, but not 3 days, upregulates the mRNA and protein expression of mTOR in the resting gastrocnemius muscle of mice, suggesting its ability to enhance protein synthesis. Consecutive-day intake of whey protein may induce constitutive alteration of the skeletal muscle, including continuous upregulation of muscle protein synthesis.
KeywordsWhey Protein IntakeResting Skeletal MuscleEnhancementProtein SynthesismTOR Pathway
Rosenberg, I.H. (1989) Summary Comments. American Journal of Clinical Nutrition, 50, 1231-1233. https://doi.org/10.1093/ajcn/50.5.1231
Walston, J.D. (2012) Sarcopenia in Older Adults. Current Opinion in Rheumatology, 24, 623-627. https://doi.org/10.1097/BOR.0b013e328358d59b
Hoffmann, C. and Weigert, C. (2017) Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations. Cold Spring Harbor Perspectives in Medicine, 7, pii: a029793. https://doi.org/10.1101/cshperspect.a029793
Fried, L.P., Tangen, C.M., Walston, J., Newman, A.B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W.J., Burke, G. and McBurnie, M.A. (2001) Cardiovascular Health Study Collaborative Research Group. Frailty in Older Adults: Evidence for a Phenotype. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 56, M146-M156. https://doi.org/10.1093/gerona/56.3.M146
Xue, Q.L., Bandeen-Roche, K., Varadhan, R., Zhou, J. and Fried, L.P. (2008) Initial Manifestations of Frailty Criteria and the Development of Frailty Phenotype in the Women’s Health and Aging Study II. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 63, 984-990. https://doi.org/10.1093/gerona/63.9.984
Borst, S.E. (2004) Interventions for Sarcopenia and Muscle Weakness in Older People. Age and Ageing, 33, 548-555. https://doi.org/10.1093/ageing/afh201
Perry, C.G.R., Lally, J., Holloway, G.P., Heigenhauser, G.J., Bonen, A. and Spriet, L.L. (2010) Repeated Transient mRNA Bursts Precede Increases in Transcriptional and Mitochondrial Proteins during Training in Human Skeletal Muscle. Journal of Physiology, 588, 4795-4810. https://doi.org/10.1113/jphysiol.2010.199448
Saxton, R.A. and Sabatini, D.M. (2017) mTOR Signaling in Growth, Metabolism, and Disease. Cell, 168, 960-976. https://doi.org/10.1016/j.cell.2017.02.004
Egan, B. and Zierath, J.R. (2013) Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation. Cell Metabolism, 17, 162-184. https://doi.org/10.1016/j.cmet.2012.12.012
Tang, J.E., Moore, D.R., Kujbida, G.W., Tarnopolsky, M.A. and Phillips, S.M. (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. Journal of Applied Physiology, 107, 987-992. https://doi.org/10.1152/japplphysiol.00076.2009
Burd, N.A., Yang, Y., Moore, D.R., Tang, J.E., Tarnopolsky, M.A. and Phillips, S.M. (2012) Greater Stimulation of Myofibrillar Protein Synthesis with Ingestion of Whey Protein Isolate v. Micellar Casein at Rest and after Resistance Exercise in Elderly Men. British Journal of Nutrition, 108, 958-962. https://doi.org/10.1017/S0007114511006271
Kim, D.H., Sarbassov, D.D., Ali, S.M., King, J.E., Latek, R.R., Erdjument-Bromage, H., Tempst, P. and Sabatini, D.M. (2002) mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex That Signals to the Cell Growth Machinery. Cell, 110, 163-175. https://doi.org/10.1016/S0092-8674(02)00808-5
Kim, D.H., Sarbassov, D.D., Ali, S.M., Latek, R.R., Guntur, K.V., Erdjument-Bromage, H., Tempst, P. and Sabatini, D.M. (2003) GβL, a Positive Regulator of the Rapamycin-Sensitive Pathway Required for the Nutrient-Sensitive Interaction between Raptor and mTOR. Molecular Cell, 11, 895-904. https://doi.org/10.1016/S1097-2765(03)00114-X
Hara, K., Maruki, Y., Long, X., Yoshino, K., Oshiro, N., Hidayat, S., Tokunaga, C., Avruch, J. and Yonezawa, K. (2002) Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action. Cell, 110, 177-189. https://doi.org/10.1016/S0092-8674(02)00833-4
Biolo, G., Maggi, S.P., Williams, B.D., Tipton, K.D. and Wolfe, R.R. (1995) Increased Rates of Muscle Protein Turnover and Amino Acid Transport after Resistance Exercise in Humans. American Journal of Physiology, 268, E514-E520. https://doi.org/10.1152/ajpendo.1995.268.3.E514
Phillips, S.M., Tipton, K.D., Aarsland, A., Wolfe, S.E. and Wolfe, R.R. (1997) Mixed Muscle Protein Synthesis and Breakdown after Resistance Exercise in Humans. American Journal of Physiology, 273, E99-E107. https://doi.org/10.1152/ajpendo.1997.273.1.E99
Phillips, S.M., Tipton, K.D., Ferrando, A.A. and Wolfe, R.R. (1999) Resistance Training Reduces the Acute Exercise-Induced Increase in Muscle Protein Turnover. American Journal of Physiology, 276, E118-E124. https://doi.org/10.1152/ajpendo.1999.276.1.E118
Tipton, K.D., Elliott, T.A., Cree, M.G., Wolf, S.E., Sanford, A.P. and Wolfe, R.R. (2004) Ingestion of Casein and Whey Proteins Result in Muscle Anabolism after Resistance Exercise. Medicine and Science in Sports Exercise, 36, 2073-2081. https://doi.org/10.1249/01.MSS.0000147582.99810.C5
Haraguchi, F.K., de Brito Magalhães, C.L., Neves, L.X., dos Santos, R.C., Pedrosa, M.L. and Silva, M.E. (2014) Whey Protein Modifies Gene Expression Related to Protein Metabolism Affecting Muscle Weight in Resistance-Exercised Rats. Nutrition, 30, 876-881. https://doi.org/10.1016/j.nut.2013.12.007
Kumar, V., Selby, A., Rankin, D., Patel, R., Atherton, P., Hildebrandt, W., Williams, J., Smith, K., Seynnes, O., Hiscock, N. and Rennie, M.J. (2008) Age-Related Differences in the Dose-Response Relationship of Muscle Protein Synthesis to Resistance Exercise in Young and Old Men. Journal of Physiology, 587, 211-217. https://doi.org/10.1113/jphysiol.2008.164483
Kraemer, W.J., Marchitelli, L., Gordon, S.E., Harman, E., Dziados, J.E., Mello, R., Frykman, P., McCurry, D. and Fleck, S.J. (1990) Hormonal and Growth Factor Responses to Heavy Resistance Exercise Protocols. Journal of Applied Physiology, 69, 1442-1450. https://doi.org/10.1152/jappl.1990.69.4.1442
Barker, D.J. and Osmond, C. (1986) Infant Mortality, Childhood Nutrition, and Ischaemic Heart Disease in England and Wales. The Lancet, 1, 1077-1081. https://doi.org/10.1016/S0140-6736(86)91340-1
Barker, D.J., Winter, P.D., Osmond, C., Margetts, B. and Simmonds, S.J. (1989) Weight in Infancy and Death from Ischaemic Heart Disease. The Lancet, 2, 577-580. https://doi.org/10.1016/S0140-6736(89)90710-1
Barker, D.J., Gluckman, P.D., Godfrey, K.M., Harding, J.E., Owens, J.A. and Robinson, J.S. (1993) Fetal Nutrition and Cardiovascular Disease in Adult Life. The Lancet, 341, 938-941. https://doi.org/10.1016/0140-6736(93)91224-A
Gluckman, P.D. and Hanson, M.A. (2004) Living with the Past: Evolution, Development, and Patterns of Disease. Science, 305, 1733-1736. https://doi.org/10.1126/science.1095292