Journal of Nutrition EB Program 2010

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supporting Material
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Anthony, T. G.
Right arrow Articles by McNurlan, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Anthony, T. G.
Right arrow Articles by McNurlan, M. A.
© 2007 The American Society for Nutrition J. Nutr. 137:357-362, February 2007

Biochemical, Molecular, and Genetic Mechanisms

Feeding Meals Containing Soy or Whey Protein after Exercise Stimulates Protein Synthesis and Translation Initiation in the Skeletal Muscle of Male Rats1,3

Tracy G. Anthony2,4,*, Brent J. McDaniel4, Peter Knoll4, Piyawan Bunpo4, Greg L. Paul5 and Margaret A. McNurlan6

4 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-Evansville, Evansville, IN 47712; 5 The Solae Company, St. Louis, MO 63188; and 6 Department of Surgery, State University of New York-Stony Brook, NY 11790

* To whom correspondence should be addressed. E-mail: tganthon{at}iupui.edu.


   ABSTRACT
TOP
 ABSTRACT
Introduction
 Experimental Design and Methods
 Results
 Discussion
 LITERATURE CITED
 
The purpose of this investigation was to compare the early response of skeletal muscle protein synthesis and translation initiation following the ingestion of different protein sources after endurance exercise. Treadmill-acclimated rats were designated as either nonexercised controls (NEX) or treadmill exercised for 2 h at 26 m/min (~75% VO2max) and then fed either carbohydrate only (EC), carbohydrate plus soy protein (ES), or carbohydrate plus whey protein (EW). One hour after exercise, serum insulin concentrations in EC, ES, and EW were greater than in NEX (P < 0.05); the concentration in EW was greater than in EC, with that in ES intermediate. Serum concentrations of branched-chain amino acids in ES and EW were higher than in EC, but serum leucine and isoleucine in EW were higher than in ES (P < 0.05). Nevertheless, both ES and EW promoted the fractional rate of skeletal muscle protein synthesis significantly more than EC. Likewise, compared with EC, both ES and EW increased formation of the mRNA cap binding complex eIF4F and stimulated phosphorylation of the translational repressor, 4E-BP1, the 70kD ribosomal protein S6 kinase (S6K1), and the mammalian target of rapamycin (mTOR) kinase at serine 2448. On the other hand, phosphorylation of S6K1 and mTOR was greater in EW than in ES (P < 0.05). In conclusion, general protein synthesis and the mRNA cap binding step are promoted comparably by soy protein and whey protein in the skeletal muscle of exercised rats. Furthermore, the data suggest that mTOR signaling in skeletal muscle is acutely responsive to physiological variations in dietary amino acids.


   Introduction
TOP
 ABSTRACT
 Introduction
Experimental Design and Methods
 Results
 Discussion
 LITERATURE CITED
 
Soy protein serves as an important source of nitrogen and essential amino acids for long-term maintenance in adult humans (1). Despite this, some are cautious to incorporate soy protein into their exercise regimen, due in part to confusion or controversy surrounding soy isoflavones in addition to lay media messages promoting animal-based proteins. In fact, the types of protein(s) that are the best for achieving muscle recovery after endurance exercise are not defined. Current opinions are based on studies focused on resistance exercise models (2) and/or studies that examine the digestibility or gastric emptying of a particular protein, categorizing it as "fast" (e.g., whey) or "slow" (e.g., casein) and extrapolating the influence of the protein digestion rate on protein anabolism (3,4). Metabolic studies conducted in humans examining whole body protein kinetics following the ingestion of soy or milk proteins report that dietary amino acids from soy proteins are directed toward deamination pathways and splanchnic/liver protein synthesis, resulting in lower postprandial nitrogen retention (5,6). However, these studies compare soy protein to pure casein or cow's milk (in which total milk protein content is ~80% casein). Compared with casein, soy protein is a relatively fast protein, with absorption kinetics closer to whey (2,7,8). Indeed, differences in nitrogen kinetics have been reported between whey and casein due to their digestion rate (9,10). To our knowledge, no study to date has directly compared soy protein with whey in terms of stimulating protein synthesis in skeletal muscle after ingestion.

Previous work demonstrates that treadmill exercise represses, and ingestion of a protein-containing meal or leucine alone immediately following exercise stimulates, skeletal muscle protein synthesis (11–13). These changes in global protein synthesis are driven at the level of mRNA translation initiation by altering the formation of eukaryotic initiation factor (eIF)7 4F, a complex of translation factors important in the selection and binding of mRNA to the small ribosomal subunit. The formation of eIF4F is regulated in part by a kinase named mammalian target of rapamycin (mTOR). The mTOR kinase is a central player in the phosphatidyl inositol 3'-OH kinase signaling pathway and integrates information on the cellular supply of nutrients and cellular energy state to downstream factors that regulate mRNA translation and other processes (14,15). mTOR is involved in the regulation of muscle growth (16,17) and, through a protein named Raptor, catalyzes the phosphorylation of the translational inhibitor, eIF4E-binding protein 1 (4E-BP1) and the p70 ribosomal protein S6 kinase (S6K1) (18). Phosphorylation of 4E-BP1 facilitates eIF4F formation by reducing its affinity for the mRNA cap binding protein, eIF4E. Activation of S6K1 results in phosphorylation of the ribosomal protein S6 and also serves as a phosphorylating kinase of mTOR at serine 2448 (19,20). Postprandial activation of 4E-BP1 and S6K1 in skeletal muscle is dependent on amino acids, and in particular, leucine (21,22).

Although much is known about the impact of individual amino acids on mTOR signaling, to our knowledge, there are no published data on comparative effects of specific dietary proteins on mTOR signaling after exercise. Thus, the purpose of the present study was to compare meals containing soy vs. whey protein on the stimulation of muscle protein synthesis and translation initiation in male rats after treadmill exercise.


   Experimental Design and Methods
TOP
 ABSTRACT
 Introduction
 Experimental Design and Methods
Results
 Discussion
 LITERATURE CITED
 
    Animals. The experimental protocol was approved by the Institutional Animal Care and Use Committee of the Indiana University School of Medicine-Evansville campus. Before each experiment, male Sprague-Dawley rats were maintained on a 12:12-h light-dark cycle with free access to a commercial pelleted soy-free diet (Harlan Teklad product TD 96155) and tap water. The commercial diet consisted of ~20% protein, 5.5% fat, and 3% fiber.

The day after arrival, all rats (initially weighing 140–150 g) began an 8-d treadmill acclimation schedule that gradually increased either speed or duration up to 26 m/min for 15 min [described in (12)]. Rats that refused to run during the acclimation period were eliminated from the study. All exercise sessions began at the beginning of the light cycle after the recording of body weight and were performed on a nonshocking motor-driven treadmill (custom designed and built by Keith Benedict of Bigfoot Industries). On the day of the experiment, treadmill-acclimated rats (n = 6–8 per group) remained in their cages (nonexercise controls, NEX) or were exercised and then fed 1 of the following 3 meals immediately after the experimental run: carbohydrate in the form of 50% sucrose plus 50% maltodextrose (EC); a mixed meal containing ~20% soy protein (ES); or a mixed meal containing ~20% whey protein (EW). The macronutrient and amino acid composition of the diets are listed in Tables 1 and 2. There was no added fat, vitamins, or minerals to the diets, only what remained associated with the isolated or concentrated protein naturally following commercial preparation. As expected, the carbohydrate-only and the whey protein contained no isoflavones, whereas the soy protein isolate contained 0.16 mg/g product aglycone units. A 2nd soy group, consisting of a soy protein concentrate high in naturally occurring isoflavones (0.63 mg/g product aglycone units) was originally analyzed separately from the other 3 exercised groups to examine whether the isoflavone content of soy protein altered any metabolic or molecular responses. However, all measured variables in the 2 soy groups did not differ from one another (Supplemental Table 1) and their statistical relations to all other groups were the same; therefore, the 2 soy groups were combined in the final data presentation. The carbohydrate source was a 50:50 sucrose-maltodextrin dry mixture reconstituted in water at room temperature on the day of oral administration. Carbohydrate was chosen instead of water or saline to serve as the exercise control group in accounting for the effect of insulin on muscle protein synthesis, because insulin has been reported to stimulate protein synthesis in young pigs, and the effect of leucine on mTOR signaling is maximized by the presence of insulin (23,24). The source of whey protein was Hillmar 8010 Instantized Whey Protein Concentrate (Hilmar Cheese). All diets were provided by The Solae Company.


View this table:
[in this window]
[in a new window]

  		TABLE 1 Macronutrient composition of postexercise meals

 

View this table:
[in this window]
[in a new window]

  		TABLE 2 Amino acid concentration of postexercise meals

 
Food was removed from exercised rats 7 h before the experimental run to reduce fecal elimination during exercise. The experimental run consisted of 2 h of treadmill running at 26 m/min, previously shown to significantly depress muscle protein synthesis and translation initiation 1 h after exercise (12). At the end of the exercise bout, rats were administered an isocaloric dose of their designated meal by oral gavage [44 kJ in 4 mL test dose; representing ~15% of daily energy needs as previously determined (12)] and returned to their cages. Rats were allowed free access to water, but no food was available beyond the defined postexercise meals. Nonexercised rats received a "postexercise" oral gavage of 4 mL water and were freely fed beforehand. All rats were killed 60 min after gavage.

    Administration of metabolic tracer and sample collection. Ten minutes before killing, a bolus dose (250 mg/kg body weight, 25 g/L) of phenylalanine labeled with deuterium ([2H5]Phe, Cambridge Isotope Laboratories) was injected via the tail vein for the in vivo measurement of skeletal muscle (gastrocnemius + plantaris) protein synthesis as previously described (25,26). One hour following meal administration, rats were decapitated and blood was collected from the neck into prechilled tubes and allowed to clot on ice for 1 h and then centrifuged at 1800 x g for 10 min (4°C) to obtain serum. The right gastrocnemius and plantaris were rapidly excised and immediately frozen in liquid nitrogen before storage in a –80°C freezer. The left hind limb muscles were weighed and homogenized in 7 volumes of buffer A [20 mmol/L N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (pH 7.4), 100 mmol/L KCl, 0.2 mmol/L EDTA, 2 mmol/L ethylene glycol-bis(ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid, 1 mmol/L dithiothreitol, 50 mmol/L NaF, 50 mmol/L ß-glycerophosphate, 0.1 mmol/L phenylmethylsulfonyl fluoride, 1 mmol/L benzamidine, and 0.5 mmol/L sodium vanadate] with a Polytron homogenizer. The homogenate was centrifuged at 10,000 x g for 10 min at 4°C and the resulting supernatant was used for determination of protein expression and activity as described below.

    Serum measurements. Serum samples were stored at –20°C or sent frozen to the Indiana University School of Medicine Quantitative Amino Acid Core Facility (under the direction of Edward Liechty, M.D.) for the determination of amino acid profiles by the ninhydrin method, using standard ion exchange chromatography with a Beckman 6300 automated amino acid analyzer. Serum insulin was measured using a commercial radioimmunoassay kit for rat insulin (Linco).

    Measurement of protein synthesis. The rate of protein synthesis in individual tissues was measured by the incorporation of injected [2H5]phenylalanine into muscle proteins (25,26). The determination of [2H5]Phe enrichment in plasma samples and in samples of hydrolyzed muscle protein has been previously described (25,26). The enrichment of [2H5]Phe in the muscle free amino acid pool was measured by GC-MS of the t-butyldimethylsilyl derivative under electron impact and selective ion recording (26). The fractional rates of protein synthesis, FSR, defined as the percentage of tissue protein renewed each day, was calculated according to the formula:

Formula

where t is the time interval between injection and cooling of sampled tissue, expressed in days, and Eb and Ea are the enrichments of [2H5]Phe in hydrolyzed tissue protein and in muscle free amino acids, respectively.

    Quantitation of eIF4E, 4E-BP1·eIF4E, and eIF4G·eIF4E complexes. The association of 4E-BP1 and eIF4G with eIF4E in muscle extracts was examined by protein immunoblot analysis after affinity purification of the mRNA cap binding protein in 10,000 x g supernatants with m7GTP-Sepharose 4B (Amersham Pharmacia Biotech). Muscle extract of equal protein concentration was added to prewashed and pre-equilibrated m7GTP-Sepharose 4B in buffer A. Following incubation for 1 h with mixing at 4°C, columns were washed 3 times with 1.5 mL ice cold buffer A. The resin was then resuspended in 0.1 mL of SDS sample buffer, boiled for 3 min and centrifuged at 10,000 x g for 5 min. The resulting supernatant was loaded onto polyacrylamide gels for SDS-PAGE and subsequent electrotransfer onto PVDF membranes. Membranes were blotted using a rabbit polyclonal antibody to either eIF4E (Cell Signaling Technology), eIF4G (Santa Cruz Biotechnology), or 4E-BP1 (Santa Cruz Biotechnology), as described previously (27).

    Phosphorylation of 4E-BP1, S6K1 and mTOR. Muscle supernatants were subjected to protein immunoblot analysis as described previously (27,28), using a rabbit polyclonal antibody to 4E-BP1 (Bethyl Labs) and a rabbit polyclonal S6K1 antibody (Santa Cruz Biotechnology). Phosphorylation of mTOR at Ser2448 was detected using an antiphospho Ser2448 mTOR antibody (Cell Signaling Technology) and expressed as a ratio of total mTOR expression, determined using an anti-mTOR antibody (Cell Signaling Technology).

    Statistical analysis. All data were analyzed by the STATISTICA statistical software package for the Macintosh, volume II (StatSoft). A 1-way ANOVA was performed with treatment group as the independent variable. When a significant overall effect was detected, differences among individual means were assessed using Tukey's Unequal Sample Size Highly Significant Difference post hoc test. The level of significance was set at P < 0.05 for all statistical tests. Values in the text are means ± SEM.


   Results
TOP
 ABSTRACT
 Introduction
 Experimental Design and Methods
 Results
Discussion
 LITERATURE CITED
 
In this study, we compared soy protein to whey protein in terms of the short-term recovery of muscle protein synthesis and translation initiation in skeletal muscle following endurance exercise. Whereas the 2 proteins were delivered so as to contain similar amounts of total nitrogen, the amount of each amino acid consumed varied according to the source profile. The total amount of indispensable AA in the soy products (g/100 g protein) were ~85% that of whey, with lower amounts of methionine, leucine, isoleucine, valine, lysine, tryptophan, and threonine and higher levels of arginine, histidine, and phenylalanine (Table 2).

In the EC group, serum insulin was 46% greater than in NEX (P < 0.05, Table 3). The insulin concentration in EW was significantly greater than in EC and that in ES was intermediate. Serum concentrations of essential amino acids were generally reduced in EC compared with NEX. On the other hand, both ES and EW had higher concentrations of threonine, lysine, leucine, isoleucine, and valine than EC, and serum concentrations of threonine, histidine, isoleucine, leucine, and valine were the same as or greater than NEX. Serum alanine, asparagine, and glutamine in ES and EW also were greater than in EC. Of note, serum leucine and isoleucine concentrations were higher in EW than in ES.


View this table:
[in this window]
[in a new window]

  		TABLE 3 Serum amino acid and insulin concentrations in male rats 1 h after feeding postexercise meals1

 
Feeding carbohydrate to EC after treadmill exercise resulted in muscle protein synthesis rates significantly less than in NEX (Fig. 1). In contrast, both ES and EW were effective at promoting general protein synthesis in skeletal muscle after treadmill exercise. Indeed, muscle FSR in ES and EW did not differ from one another and were greater than in EC.


Figure 1
View larger version (17K):
[in this window]
[in a new window]

  		Figure 1  The fractional rate of skeletal muscle protein synthesis is promoted similarly in male rats 1 h after postexercise feeding of meals containing either soy protein or whey. Data are means ± SEM, n = 6–12. Means not sharing a common letter differ, P < 0.05.

 
Formation of the eIF4F complex was evaluated by determining the association of eIF4E with 4E-BP1 (Fig. 2A) vs. eIF4G (Fig. 2B). Consistent with global rates of muscle protein synthesis, EC demonstrated decreased eIF4F formation after exercise that was represented by a reduction in the eIF4G·eIF4E complex and increase in the 4E-BP1·eIF4E complex compared with NEX. Both protein-containing meals reversed these effects; ES and EW did not differ from NEX.


Figure 2
View larger version (35K):
[in this window]
[in a new window]

  		Figure 2  Both soy and whey protein promote the mRNA binding step, but whey-fed rats demonstrate higher phosphorylation of p70 S6K1 and mTOR 1 h after exercise. Phosphorylation of 4E-BP1 (A). Phosphorylation of S6K1 (B). Association of eIF4E with 4E-BP1 (C). Association of eIF4E with eIF4G (D). Phosphorylation of mTOR at serine 2448 (E). Data are means ± SEM; n = 4–12. Means without a common letter differ, P < 0.05.

 
To evaluate the effects of soy vs. whey on mTOR signaling, the phosphorylation of 4E-BP1 and S6K1 were analyzed. Carbohydrate ingestion by EC following prolonged treadmill running reduced 4E-BP1 phosphorylation compared with NEX (Fig. 2C). In contrast, the ES and EW groups did not differ from NEX. ES and EW had greater phosphorylation of S6K1 than EC (Fig. 2D). However, EW exhibited significant hyperphosphorylation of S6K1 relative to all other groups. Phosphorylation of mTOR at Ser2448 was greater in EW than in ES and both of these were greater than EC and NEX, which did not differ (Fig. 2E). In summary, both soy protein and whey protein promoted general muscle protein synthesis and eIF4F formation after treadmill exercise. On the other hand, phosphorylation of S6K1 and mTOR were most responsive to whey protein ingestion.


   Discussion
TOP
 ABSTRACT
 Introduction
 Experimental Design and Methods
 Results
 Discussion
LITERATURE CITED
 
To our knowledge, this study is the first to compare a vegetable-based protein to an animal-based protein in promoting the recovery of skeletal muscle protein synthesis and mRNA translation initiation factor activity after endurance exercise. We found that general protein synthesis and eIF4F formation were comparable among rats fed the different protein-containing meals after exercise. In contrast, rats fed whey protein demonstrated enhanced mTOR phosphorylation via S6K1 compared with those fed soy protein. These latter findings suggest that mTOR signaling in skeletal muscle is acutely responsive to variations in circulating insulin and AA concentrations following ingestion of intact dietary proteins.

As in our previous work, we found that high-intensity treadmill running decreased muscle protein synthesis after exercise. In support of our findings, Williamson et al. (13) found that 10–30 min of intense treadmill running in mice caused the disaggregation of polysomes into free ribosomes. In addition, 90 min of exercise on a cycle ergometer at 67% VO2 max in healthy men reportedly increased phosphorylation of eukaryotic elongation factor 2 (eEF2), indicating decreased eEF2 activity and mRNA translation (29). These results support the concept that high intensity aerobic exercise stymies muscle anabolism in the short term. This is in contrast to less intense aerobic exercise, which reportedly increases muscle and plasma protein synthesis in humans (30).

We previously found that consumption of a protein-containing meal or leucine alone stimulates muscle protein synthesis after exercise (11,12). The current results extend our previous findings to include soy protein as an effective means to stimulate muscle protein synthesis. Also consistent with our previous work, we found that protein feeding after exercise does not stimulate muscle protein synthesis equal to that in sedentary-fed rats but, rather, recovers synthesis rates to a slightly lower level. This lower level was previously shown to reflect nonexercised rats that were not fed for 10 h (12). Perhaps postexercise muscle protein synthesis rates are higher at an earlier point after feeding, insofar as maximal stimulation of muscle protein synthesis following leucine ingestion occurs at 30 min postingestion (23). Or, perhaps if more energy were provided, a greater stimulation might have been achieved. Additional time-course and dose-response studies are needed to fully answer these questions.

There is little information in the exercise literature, particularly with respect to aerobic exercise, on divergent responses to different protein sources. Soy and whey were the chosen comparisons because of their similar digestibility and absorption kinetics. The temporal release of amino acids into the blood from both soy protein and whey protein are relatively fast, as both are soluble at low pH. In contrast, casein clots when in contact with stomach acid, providing a much slower release of amino acids into the circulation (3,31–33). Metabolic studies in subjects at rest indicate that prandial responses to ingestion or infusion of soy protein differ greatly from responses to milk (3,7,33,34). The current study concurs that the circulating amino acid profile differs following ingestion of soy protein vs. whey, with lower circulating concentrations of the BCAA and in particular, leucine. Nevertheless, muscle protein synthesis rates were comparable in the ES and EW groups. Additional time-course studies are required to determine whether the similar responses reported here are maintained over time.

Recent studies demonstrate that physiological increases in circulating leucine stimulate mTOR signaling in muscle (21). In addition, leucine alone or as a supplement has been shown to stimulate muscle protein synthesis after exercise in both endurance and resistance exercise models (11,35). In contrast to muscle protein synthesis and eIF4F formation, phosphorylation of S6K1 is highly responsive to physiological differences in leucine concentrations. Signaling through S6K1 is involved in regulating cell size and is required for muscle hypertrophy (17,36). S6K1 is also a major effector of mTOR phosphorylation at Ser2448 in response to both mitogens and nutrients (19,20). Both amino acids (leucine) and insulin have been reported to stimulate phosphorylation of mTOR at Ser2448 (37,38). In the current study, both soy and whey meals increased circulating concentrations of insulin and leucine, with whey protein producing the highest concentrations of both. As such, it follows that phosphorylation of mTOR at Ser2448 followed this pattern. It is unknown if the differential response in mTOR signaling to soy protein and whey protein translates to differences in muscle growth or function, particularly insofar as eIF4F complex formation and global protein synthesis in skeletal muscle did not differ between the ES and EW groups. Whether mTOR signaling more directly or accurately reflects the growth status of myofibers compared with the measurement of protein synthesis and eIF4F complex formation is also unclear and requires further study.

Taken in total, the current study suggests that both soy and whey proteins are useful sources of protein for muscle support following aerobic exercise. The concept of testing mixes of different dietary proteins to achieve and/or maximally sustain an optimal BCAA profile remains to be tested. It also remains to be determined how formation of the mRNA cap binding complex and mTOR signaling change over time in relation to global rates of protein synthesis following ingestion of soy, whey, and other proteins. Finally, additional research is needed to understand which classes of proteins within skeletal muscle are directed by eIF4F complex formation vs. mTOR signaling, particularly when these measurements diverge from each other.


   ACKNOWLEDGMENTS
 
The technical assistance of George Casella and Judy Cundiff and scientific counsel of Giuseppe Caso are gratefully acknowledged.


   FOOTNOTES
 
1 The work described in this article was funded by The Solae Company, St. Louis, MO. Back

2 T. G. Anthony received travel support by The Solae Company to present this work at the 6th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, held in Chicago, IL. Back

3 Supplemental Table 1 is available with the online posting of this paper at jn.nutrition.org. Back

7 Abbreviations used: eIF, eukaryotic initiation factor; 4E-BP1, eIF4E-binding protein 1; EC, postexercise 100% carbohydrate meal; ES, postexercise carbohydrate plus soy protein; EW, postexercise carbohydrate plus whey protein; NEX, nonexercise controls; mTOR, mammalian target of rapamycin; S6K1, ribosomal protein S6 kinase 1. Back

Manuscript received 27 July 2006. Initial review completed 21 August 2006. Revision accepted 3 December 2006.


   LITERATURE CITED
TOP
 ABSTRACT
 Introduction
 Experimental Design and Methods
 Results
 Discussion
 LITERATURE CITED
 

1. Istfan N, Murray E, Janghorbani M, Evans W, Young V. The nutritional value of a soy protein concentrate (STAPRO-3200) for long-term protien nutritional maintenance in young men. J Nutr. 1983;113:2524–34.[Abstract/Free Full Text]

2. Tipton KD, Wolfe RR. Protein and amino acids for athletes. J Sports Sci. 2004;22:65–79.[Medline]

3. Hara H, Nishikawa H, Kiriyama S. Different effects of casein and soyabean protein on gastric emptying of protein and small intestinal transit after spontaneous feeding of diets in rats. Br J Nutr. 1992;68:59–66.[Medline]

4. Mariotti F, Mahe S, Benamouzig R, Luengo C, Dare S, Gaudichon C, Tome D. Nutritional value of [15]N-soy protein isolate assessed from ileal digestibility and postprandial protein utilization in humans. J Nutr. 1999;129:1992–7.[Abstract/Free Full Text]

5. Bos C, Metges C, Gaudichon C, Petzke K, Pueyo M, Morens C, Everwand J, Benamouzig R, Tome D. Postprandial kinetics of dietary amino acids are the main determinant of their metabolism after soy or milk protein ingestion in humans. J Nutr. 2003;133:1308–15.[Abstract/Free Full Text]

6. Luiking YC, Deutz NE, Jakel M, Soeters PB. Casein and soy protein meals differentially affect whole-body and splanchnic protein metabolism in healthy humans. J Nutr. 2005;135:1080–7.[Abstract/Free Full Text]

7. Fouillet H, Mariotti F, Gaudichon C, Bos C, Tome D. Peripheral and splanchnic metabolism of dietary nitrogen are differently affected by the protein source in humans as assessed by compartmental modeling. J Nutr. 2002;132:125–33.[Abstract/Free Full Text]

8. Fruhbeck G. Protein metabolism. Slow and fast dietary proteins. Nature. 1998;391:843–5.[Medline]

9. Dangin M, Boirie Y, Guillet C, Beaufrere B. Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr. 2002;132:3228S–33S.[Abstract/Free Full Text]

10. Dangin M, Guillet C, Garcia-Rodenas C, Gachon P, Bouteloup-Demange C, Reiffers-Magnani K, Fauquant J, Ballevre O, Beaufrere B. The rate of protein digestion affects protein gain differently during aging in humans. J Physiol. 2003;549:635–44.[Abstract/Free Full Text]

11. Anthony JC, Anthony TG, Layman DK. Leucine supplementation enhances skeletal muscle recovery in rats following exercise. J Nutr. 1999;129:1102–6.[Abstract/Free Full Text]

12. Gautsch TA, Anthony JC, Paul GL, Kimball SR, Layman DK, Jefferson LS. Availability of eIF4E regulates skeletal muscle protein synthesis during recovery from exercise. Am J Physiol. 1998;274:C406–C14.

13. Williamson DL, Kubica N, Kimball SR, Jefferson LS. Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscle. J Physiol. 2006;573:497–510.[Abstract/Free Full Text]

14. Gingras A, Raught B, Sonenberg N. mTOR signaling to translation. Curr Top Microbiol Immunol. 2004;279:169–97.[Medline]

15. Tokunaga C, Yoshino K, Yonezawa K. mTOR integrates amino acid- and energy-sensing pathways. Biochem Biophys Res Commun. 2004;313:443–6.[Medline]

16. Bodine S, Stitt T, Gonzalez M, Kline W, Stover G, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence J, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 2001;3:1014–9.[Medline]

17. Park IH, Erbay E, Nuzzi P, Chen J. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1. Exp Cell Res. 2005;309:211–9.[Medline]

18. Kim D, Sarbassov D, Ali S, King J, Latek R, Erdjument-Bromage H, Tempst P, Sabatini D. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 2002;110:163–75.[Medline]

19. Chiang GG, Abraham RT. Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase. J Biol Chem. 2005;280:25485–90.[Abstract/Free Full Text]

20. Holz MK, Blenis J. Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase. J Biol Chem. 2005;280:26089–93.[Abstract/Free Full Text]

21. Escobar J, Frank JW, Suryawan A, Nguyen HV, Kimball SR, Jefferson LS, Davis TA. Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation. Am J Physiol Endocrinol Metab. 2005;288:E914–21.[Abstract/Free Full Text]

22. Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr. 2000;130:2413–9.[Abstract/Free Full Text]

23. Anthony JC, Lang CH, Crozier SJ, Anthony TG, MacLean DA, Kimball SR, Jefferson LS. Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. Am J Physiol. 2002;282:E1092–E101.

24. O'Connor PM, Bush JA, Suryawan A, Nguyen HV, Davis TA. Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs. Am J Physiol Endocrinol Metab. 2003;284:E110–9.[Abstract/Free Full Text]

25. Bark T, McNurlan M, Lang C, Garlick PJ. Increased protein synthesis after acute IGF-I or insulin infusion is localized to muscle in mice. Am J Physiol. 1998;275:E118–E23.

26. McNurlan MA, Essén P, Thorell A, Calder AG, Andersson SE, Ljungqvist O, Sandgren A, Grant I, Tjäder I, et al. Response of protein synthesis in human skeletal muscle to insulin: an investigation with L-[2H5]phenylalanine. Am J Physiol. 1994;267:E102–E8.

27. Anthony JC, Anthony TG, Kimball SR, Vary TC, Jefferson LS. Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. J Nutr. 2000;130:139–45.[Abstract/Free Full Text]

28. Anthony TG, Anthony JC, Yoshizawa F, Kimball SR, Jefferson LS. Oral administration of leucine stimulates ribosomal protein mRNA translation but not global rates of protein synthesis in the liver of rats. J Nutr. 2001;131:1171–6.[Abstract/Free Full Text]

29. Rose AJ, Broholm C, Kiillerich K, Finn SG, Proud CG, Rider MH, Richter EA, Kiens B. Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men. J Physiol. 2005;569:223–8.[Abstract/Free Full Text]

30. Sheffield-Moore M, Yeckel CW, Volpi E, Wolf SE, Morio B, Chinkes DL, Paddon-Jones D, Wolfe RR. Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise. Am J Physiol Endocrinol Metab. 2004;287:E513–22.[Abstract/Free Full Text]

31. Beaufrere B, Dangin M, Boirie Y. The "fast" and "slow" protein concept. Nestle Nutr Workshop Ser Clin Perform Programme. 2000;3:121–31.[Medline]

32. Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrere B. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA. 1997;94:14930–5.[Abstract/Free Full Text]

33. Bos C, Metges CC, Gaudichon C, Petzke KJ, Pueyo ME, Morens C, Everwand J, Benamouzig R, Tome D. Postprandial kinetics of dietary amino acids are the main determinant of their metabolism after soy or milk protein ingestion in humans. J Nutr. 2003;133:1308–15.[Abstract/Free Full Text]

34. Deutz NE, Bruins MJ, Soeters PB. Infusion of soy and casein protein meals affects interorgan amino acid metabolism and urea kinetics differently in pigs. J Nutr. 1998;128:2435–45.[Abstract/Free Full Text]

35. Koopman R, Wagenmakers AJ, Manders RJ, Zorenc AH, Senden JM, Gorselink M, Keizer HA, van Loon LJ. Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects. Am J Physiol Endocrinol Metab. 2005;288:E645–53.[Abstract/Free Full Text]

36. Thomas G. The S6 kinase signaling pathway in the control of development and growth. Biol Res. 2002;35:305–13.[Medline]

37. Proud C. Role of mTOR signalling in the control of translation initiation and elongation by nutrients. Curr Top Microbiol Immunol. 2004;279:215–44.[Medline]

38. Reynolds TH, Bodine SC, Lawrence JC, Jr. Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. J Biol Chem. 2002;277:17657–62.[Abstract/Free Full Text]




This article has been cited by other articles:


Home page
 J. Nutr.Home page
L. E. Norton, D. K. Layman, P. Bunpo, T. G. Anthony, D. V. Brana, and P. J. Garlick
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., June 1, 2009; 139(6): 1103 - 1109.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
R. Hageman, C. Severijnen, B. J. M. van de Heijning, H. Bouritius, N. van Wijk, K. van Laere, and E. M. van der Beek
A Specific Blend of Intact Protein Rich in Aspartate Has Strong Postprandial Glucose Attenuating Properties in Rats
J. Nutr., September 1, 2008; 138(9): 1634 - 1640.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
P. J. Morrison, D. Hara, Z. Ding, and J. L. Ivy
Adding protein to a carbohydrate supplement provided after endurance exercise enhances 4E-BP1 and RPS6 signaling in skeletal muscle
J Appl Physiol, April 1, 2008; 104(4): 1029 - 1036.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supporting Material
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Anthony, T. G.
Right arrow Articles by McNurlan, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Anthony, T. G.
Right arrow Articles by McNurlan, M. A.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2007 by American Society for Nutrition