Protein Blend and Casein Supplementations before Inactive Phase Similarly Activate Mechanistic Target of Rapamycin Signaling in Rat Skeletal Muscle

10.4103/CJP.CJP_31_20

Tales Sambrano Vieira；Ana P. Pinto；Gabriela Batitucci；Alisson L. da Rocha；Hugo T. Filho；Dawit A. Gonçalves；Adelino Sanchez R. da Silva；Ellen Cristini de Freitas

Micellar casein ； mTOR signaling pathway ； protein supplementation ； protein synthesis ； skeletal muscle ； whey protein

The Chinese Journal of Physiology

63卷4期（2020 / 08 / 31）

171 - 178

英文

During overnight sleep, the longest postabsorptive and inactive phase of the day causes protein catabolism and loss. However, the daytime ingestion of dairy proteins has been shown to stimulate muscle protein synthesis and growth. This study compared the effects of pre-sleep supplementation of a protein blend (PB) composed of micellar casein (MCa) and whey protein (1:1) versus isolate MCa on the plasma levels of branched-chain amino acids (BCAAs) and the activation of the mechanistic target of rapamycin (mTOR) signaling, a critical intracellular pathway involved in the regulation of muscle protein synthesis. After 10 h of fasting during the active phase, rats were fed with a single dose of PB or MCa (5.6 g protein/kg of body mass) by gavage, and samples of blood and gastrocnemius muscle were collected at 30, 90, and 450 min. PB and MCa supplementations induced an increase (~3-fold, P ＜ 0.001) of plasma BCAAs at 30 and 90 min. Most importantly, the stimulatory phosphorylation levels of mTOR and its downstream target p70 ribosomal protein S6 kinase (p70S6K) were similarly higher (~2.5-fold, P ＜ 0.001) 30 and 90 min after MCa and PB. Plasma levels of leucine, isoleucine, valine, and overall BCAAs were correlated with the activation of mTOR (P ＜ 0.001) and p70S6K (P ＜ 0.001). MCa and PB supplementations before the inactive phase of rats resulted in an anabolic milieu in the skeletal muscle by inducing a transient increase in plasma BCAAs and a similar activation of the mTOR/p70S6K axis.

1. Anthony, JC,Yoshizawa, F,Anthony, TG,Vary, TC,Jefferson, LS,Kimball, SR(2000).Leucine stimulates translation initiation in skeletal muscle of post-absorptive rats via a rapamycin-sensitive pathway.J Nutr,130,2413-2419.
2. Bassil, MS,Gougeon, R(2013).Muscle protein anabolism in type 2 diabetes.Curr Opin Clin Nutr Metab Care,16,83-88.
3. Baum, JI,Wolfe, RR(2015).The link between dietary protein intake, skeletal muscle function and health in older adults.Healthcare,3,529-543.
4. Boirie, Y,Dangin, M,Gachon, P,Vasson, MP,Maubois, JL,Beaufrère, B(1997).Slow and fast dietary proteins differently modulate postprandial protein accretion.Proc Natl Acad Sci U S A,94,14930-14935.
5. Bradfort, MM(1976).A rapid and sensitive method for the quantitation of microgan quantities of protein utilizing the principle of protein-dye binding.Anal Biochem,72,248-254.
6. Butteiger, DN,Cope, M,Liu, P,Mukherjea, R,Volpi, E,Rasmussen, BB(2013).A soy, whey and caseinate blend extends postprandial skeletal muscle protein synthesis in rats.Clin Nutr,32,585-591.
7. Chantranupong, L,Scaria, SM,Saxton, RA,Gygi, MP,Shen, K,Wyant, GA(2016).The castor protein are arginine sensors for the mTORC1 pathway.Cell,165,153-164.
8. Churchward-Venne, TA,Burd, NA,Mitchell, CJ,West, DW,Philp, A,Marcotte, GR(2012).Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men.J Physiol,590,2751-2765.
9. Crozier, SJ,Kimball, SR,Emmert, SW,Anthony, JC,Jefferson, LS(2005).Oral leucine administration stimulates protein synthesis in rat skeletal muscle.J Nutr,135,376-382.
10. Deutz, NE,Safar, A,Schutzler, S,Memelink, R,Ferrando, A,Spencer, H(2011).Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food.Clin Nutr,30,759-768.
11. Dijk, FJ,van Dijk, M,Walrand, S,van Loon, LJC,van Norren, K,Luiking, YC(2018).Differential effects of leucine and leucine‑enriched whey protein on skeletal muscle protein synthesis in aged mice.Clin Nutr ESPEN,24,127-133.
12. Drummond, MJ,Rasmussen, BB(2008).Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis.Curr Opin Clin Nutr Metab Care,11,222-226.
13. Emery, PW,Edwards, RH,Rennie, MJ,Souhami, RL,Halliday, D(1984).Protein synthesis in muscle measured in vivo in cachectic patients with cancer.Br Med J (Clin Res Ed),289,584-586.
14. Fucks, CJ,Hermans, WJH,Holwerda, AM,Smeets, JSJ,Senden, JM,Kranenburg, J(2019).Branched-chain amino acid and branched-chain ketoacid ingestion increases muscle protein synthesis rates in vivo in older adults: a double-blind, randomized trial.Am J Clin Nutr,110,862-872.
15. Glover, EI,Phillips, SM,Oates, BR,Tang, JE,Tarnopolsky, MA,Selby, A(2008).Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion.J Physiol,586,6049-6061.
16. Hamarsland, H,Nordengen, AL,Nyvik Aas, S,Holte, K,Garthe, I,Paulsen, G(2017).Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: A randomized controlled trial.J Int Soc Sports Nutr,14,43.
17. Jewell, JE,Kim, YC,Russell, RC,Yu, FX,Park, HW,Plouffe, SW(2015).Differential regulation of mTORC1 by leucine and glutamine.Science,347,194-198.
18. Kanda, A,Nakayama, K,Sanbongi, C,Nagata, M,Ikegami, S,Itoh, H(2016).Effects of whey, caseinate, or milk protein ingestion on muscle protein synthesis after exercise.Nutrients,8,339.
19. Kouw, IW,Holwerda, AM,Trommelen, J,Kramer, IF,Bastiaanse, J,Halson, SL(2017).Protein ingestion before sleep increases overnight muscle protein synthesis rates in healthy older men: A randomized controlled trial.J Nutr,147,2252-2261.
20. Marabita, M,Baraldo, M,Solagna, F,Ceelen, JJM,Sartori, R,Nolte, H(2016).S6K1 is required for increasing skeletal muscle force during hypertrophy.Cell Rep,17,501-513.
21. Norton, LE,Layman, DK,Bunpo, P,Anthony, TG,Brana, DV,Garlick, PJ(2009).The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats.J Nutr,139,1103-1109.
22. Ohanna, M,SoberingAK,Lapointe, T,Lorenzo, L,Praud, C,Petroulakis, E(2005).Atrophy of S6K1-/-skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control.Nat Cell Biol,7,286-294.
23. Paul, GL.(2009).The rationale for consuming protein blends in sports nutrition.J Am Coll Nutr,28(Suppl),464S-472S.
24. 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,93,997-1005.
25. Phillips, SM(2009).Physiologic and molecular bases of muscle hypertrophy and atrophy: impact of resistance exercise on human skeletal muscle (protein and exercise dose effects).Appl Physiol Nutr Metab,34,403-410.
26. Pinto, AP,Vieira, TS,Marafon, BB,Batitucci, G,Cabrera, EM,da Rocha, AL(2020).The combination of fasting, acute resistance exercise, and protein ingestion led to different responses of autophagy markers in gastrocnemius and liver samples.Nutrients,12,641.
27. Reidy, PT,Walker, DK,Dickinson, JM,Gundermann, DM,Drummond, MJ,Timmerman, KL(2013).Protein blend ingestion following resistance exercise promotes human muscle protein synthesis.J Nutr,143,410-416.
28. Reitelseder, S,Agergaard, J,Doessing, S,Helmark, IC,Lund, P,Kristensen, NB(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,E231-E242.
29. Res, PT,Groen, B,Pennings, B,Beelen, M,Wallis, GA,Gijsen, AP(2012).Protein ingestion before sleep improves postexercise overnight recovery.Med Sci Sports Exerc,44,1560-1569.
30. Snijders, T,Res, PT,Smeets, JS,van Vliet, S,van Kranenburg, J,Maase, K(2015).Protein ingestion before sleep increases muscle mass and strength gains during prolonged resistance-type exercise training in healthy young men.J Nutr,145,1178-1184.
31. Stokes, T,Hector, AJ,Morton, RW,McGlory, C,Phillips, SM(2018).Recent perspectives regarding the role of dietary protein for the promotion of muscle hypertrophy with resistance exercise training.Nutrients,10,180.
32. 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 (1985),107,987-992.
33. Traylor, DA,Gorissen, SHM,Hopper, H,Prior, T,McGlory, C,Phillips, SM(2019).Aminoacidemia following ingestion of native whey protein, micellar casein, and a whey-casein blend in young men.Appl Physiol Nutr Metab,44,103-106.
34. Trommelen, J,Holwerda, AM,Kouw, IW,Langer, H,Halson, SL,Rollo, I(2016).Resistance exercise augments postprandial overnight muscle protein synthesis rates.Med Sci Sports Exerc,48,2517-2525.
35. Trommelen, J,Kouw, IW,Holwerda, AM,Snijders, T,Halson, SL,Rollo, I(2018).Pre-sleep dietary protein-derived amino acids are incorporated in myofibrillar protein during postexercise overnight recovery.Am J Physiol Endocrinol Metab,314,E457-E467.
36. Wang, X,Proud, CG(2006).The mTOR pathway in the control of protein synthesis.Physiology,21,362-369.
37. Wolfe, RR(2017).Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?.J Int Soc Sports Nutr,14,30.
38. Wolfe, RR(2012).The role of dietary protein in optimizing muscle mass, function and health outcomes in older individuals.Br J Nutr,108(Suppl 2),S88-S93.