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Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033
4To whom correspondence should be addressed.
We investigated the protein synthetic response of skeletal muscle to an
orally administered dose of leucine given alone or in combination with
carbohydrate. Male rats were freely fed (F) or food deprived for
18 h; food-deprived rats were then administered saline (S),
carbohydrate (CHO), leucine (L) or a combination of carbohydrate plus
leucine (CL). CHO and CL meals were isocaloric and provided 15% of
daily energy requirements. L and CL meals each delivered 270 mg
leucine. Muscle protein synthesis in S was 65% of F (P
< 0.01) 1 h after meal administration. Concomitant with
lower rates of protein synthesis, phosphorylation of the translational
repressor, eukaryotic initiation factor (eIF)4E-binding protein 1
(4E-BP1), was less in S, leading to greater association of
4E-BP1·eIF4E, and reduced formation of the active eIF4G·eIF4E
complex compared with F (P < 0.01). Oral
administration of leucine (L or CL), but not CHO, restored protein
synthesis equal to that in F and resulted in 4E-BP1 phosphorylation
that was threefold greater than that of S (P < 0.01). Consequently, formation of 4E-BP1·eIF4E was inhibited and
eIF4G·eIF4E was not different from F. The amount of eIF4E in the
phosphorylated form was greater in S and CHO (P < 0.01) than in all other groups. In contrast, no differences in the
phosphorylation state of eIF2
or the activity of eIF2B were noted
among treatment groups. Serum insulin was elevated 2.6- and 3.7-fold in
CHO and CL, respectively, but was not different in L, compared with S
(P < 0.05). These results suggest that leucine
stimulates protein synthesis in skeletal muscle by enhancing eIF4F
formation independently of increases in serum insulin.
KEY WORDS: • leucine • protein synthesis • translation initiation • skeletal muscle • rats
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J. S. Greiwe, G. Kwon, M. L. McDaniel, and C. F. Semenkovich Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E466 - E471. [Abstract] [Full Text] [PDF]
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M. Balage, S. Sinaud, M. Prod'Homme, D. Dardevet, T. C. Vary, S. R. Kimball, L. S. Jefferson, and J. Grizard Amino acids and insulin are both required to regulate assembly of the eIF4E {middle dot} eIF4G complex in rat skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E565 - E574. [Abstract] [Full Text] [PDF]
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L. S. Jefferson and S. R. Kimball Amino Acid Regulation of Gene Expression J. Nutr., September 1, 2001; 131(9): 2460S - 2466. [Abstract] [Full Text] [PDF]
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E. Blomstrand and B. Saltin BCAA intake affects protein metabolism in muscle after but not during exercise in humans Am J Physiol Endocrinol Metab, August 1, 2001; 281(2): E365 - E374. [Abstract] [Full Text] [PDF]
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Z. Liu, L. A. Jahn, W. Long, D. A. Fryburg, L. Wei, and E. J. Barrett Branched Chain Amino Acids Activate Messenger Ribonucleic Acid Translation Regulatory Proteins in Human Skeletal Muscle, and Glucocorticoids Blunt This Action J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2136 - 2143. [Abstract] [Full Text]
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T. G. Anthony, J. C. Anthony, F. Yoshizawa, S. R. Kimball, and L. S. Jefferson Oral Administration of Leucine Stimulates Ribosomal Protein mRNA Translation but Not Global Rates of Protein Synthesis in the Liver of Rats J. Nutr., April 1, 2001; 131(4): 1171 - 1176. [Abstract] [Full Text]
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 G. GARIBOTTO, A. SOFIA, A. CANEPA, S. SAFFIOTI, P. SACCO, M. R. SALA, L. DERTENOIS, N. PASTORINO, G. DEFERRARI, and R. RUSSO Acute Effects of Peritoneal Dialysis with Dialysates Containing Dextrose or Dextrose and Amino Acids on Muscle Protein Turnover in Patients with Chronic Renal Failure J. Am. Soc. Nephrol., March 1, 2001; 12(3): 557 - 567. [Abstract] [Full Text]
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S. M. Hutson and R. A. Harris Introduction J. Nutr., March 1, 2001; 131(3): 839S - 840. [Full Text]
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R. A. Harris, R. Kobayashi, T. Murakami, and Y. Shimomura Regulation of Branched-Chain {{alpha}}-Keto Acid Dehydrogenase Kinase Expression in Rat Liver J. Nutr., March 1, 2001; 131(3): 841S - 845. [Abstract] [Full Text]
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J. C. Anthony, T. G. Anthony, S. R. Kimball, and L. S. Jefferson Signaling Pathways Involved in Translational Control of Protein Synthesis in Skeletal Muscle by Leucine J. Nutr., March 1, 2001; 131(3): 856S - 860. [Abstract] [Full Text]
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C. J. Lynch Role of Leucine in the Regulation of mTOR by Amino Acids: Revelations from Structure-Activity Studies J. Nutr., March 1, 2001; 131(3): 861S - 865. [Abstract] [Full Text]
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E. Volpi, B. Mittendorfer, B. B. Rasmussen, and R. R. Wolfe The Response of Muscle Protein Anabolism to Combined Hyperaminoacidemia and Glucose-Induced Hyperinsulinemia Is Impaired in the Elderly J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4481 - 4490. [Abstract] [Full Text]
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C. H. Lang, R. A. Frost, V. Kumar, and T. C. Vary Impaired myocardial protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4F Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1029 - E1038. [Abstract] [Full Text] [PDF]
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S. R. Kimball, L. S. Jefferson, H. V. Nguyen, A. Suryawan, J. A. Bush, and T. A. Davis Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1080 - E1087. [Abstract] [Full Text] [PDF]
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O. J. Shah, J. C. Anthony, S. R. Kimball, and L. S. Jefferson Glucocorticoids oppose translational control by leucine in skeletal muscle Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1185 - E1190. [Abstract] [Full Text] [PDF]
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D. Dardevet, C. Sornet, M. Balage, and J. Grizard Stimulation of In Vitro Rat Muscle Protein Synthesis by Leucine Decreases with Age J. Nutr., November 1, 2000; 130(11): 2630 - 2635. [Abstract] [Full Text] [PDF]
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O. J. Shah, J. C. Anthony, S. R. Kimball, and L. S. Jefferson 4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E715 - E729. [Abstract] [Full Text] [PDF]
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J. C. Anthony, F. Yoshizawa, T. G. Anthony, T. C. Vary, L. S. Jefferson, and S. R. Kimball Leucine Stimulates Translation Initiation in Skeletal Muscle of Postabsorptive Rats via a Rapamycin-Sensitive Pathway J. Nutr., October 1, 2000; 130(10): 2413 - 2419. [Abstract] [Full Text]
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L. J. C. van Loon, M. Kruijshoop, H. Verhagen, W. H. M. Saris, and A. J. M. Wagenmakers Ingestion of Protein Hydrolysate and Amino Acid-Carbohydrate Mixtures Increases Postexercise Plasma Insulin Responses in Men J. Nutr., October 1, 2000; 130(10): 2508 - 2513. [Abstract] [Full Text]
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S. R. Kimball, P. A. Farrell, H. V. Nguyen, L. S. Jefferson, and T. A. Davis Developmental decline in components of signal transduction pathways regulating protein synthesis in pig muscle Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E585 - E592. [Abstract] [Full Text] [PDF]
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