Oral leucine administration stimulates protein synthesis in rat skeletal muscle
Open accessAbstract
Oral administration of a single bolus of leucine in an amount equivalent to the daily intake (1.35 g/kg body wt) enhances skeletal muscle protein synthesis in food-deprived rats. To elucidate whether smaller amounts of leucine can also stimulate protein synthesis, rats were administered the amino acid at concentrations ranging from 0.068 to 1.35 g/kg body wt by oral gavage. Thirty minutes following the administration of doses of leucine as low as 0.135 g/kg body wt, skeletal muscle protein synthesis was significantly greater than control values. The increase in protein synthesis was associated with changes in the regulation of biomarkers of mRNA translation initiation as evidenced by upregulated phosphorylation of the translational repressor, eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), the association of eIF4G with the mRNA cap binding protein eIF4E, and the phosphorylation of the 70-kDa ribosomal protein S6 kinase. Alterations in the phosphorylation of eIF4G, as well as the association of 4E-BP1 with eIF4E, were observed following leucine administration; however, these changes appeared to be biphasic with maximal changes occurring when circulating insulin concentrations were elevated. Thus it appears that leucine administration affects mRNA translation and skeletal muscle protein synthesis through modulation of multiple biomarkers of mRNA translation. The ability of small doses of leucine to stimulate skeletal muscle protein synthesis suggests that future research on the regulation of skeletal muscle protein synthesis by orally administered leucine will be feasible in humans.
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As leucine enters the muscle it triggers protein synthesis largely through its ability to activate mTORC1.
“As leucine enters the muscle it acts to trigger protein synthesis largely through its ability to activate mTORC1 [19].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [19]
The Discussion (page unavailable) reports that oral leucine stimulates skeletal muscle protein synthesis in food-deprived rats and describes an mTOR-dependent effect on a translation-initiation regulator. It also says another leucine-induced change involves both mTOR-dependent and mTOR-independent pathways, and that the study cannot determine which pathways mediate the increase in protein synthesis. It therefore does not establish that activation of mTORC1 accounts for most of that increase. (LLM, conf=0.87)
Experimental — accuracy not yet measuredOnly a fraction of maximal mTORC1 activity (~30%) is required to fully saturate muscle protein synthesis.
“Furthermore, only a fraction of maximal mTORC1 activity (~30%) is required to fully saturate muscle protein synthesis [98,99].”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [98]
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“As leucine enters the muscle it acts to trigger protein synthesis largely through its ability to activate mTORC1 [19].”
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- Authors
- Crozier, S. J., Kimball, S. R., Emmert, S. W., Anthony, J. C., & Jefferson, L. S.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Jefferson, Leonard S.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 135
- Issue
- 3
- Pages
- 376-382
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2165232899
- Cited by
- 371
- References
- 49
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 12 · 2022: 14 · 2021: 10 · 2020: 17 · 2019: 14 · 2018: 24 · 2017: 18 · 2016: 38 · 2015: 23 · 2014: 28 · 2013: 22 · 2012: 29
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pennsylvania State University
- Deutsches Krebsforschungszentrum
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-15658, R01DK015658)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- leucine, skeletal muscle protein synthesis, mRNA translation, eIF4E, 4E-BP1, eIF4G, S6K, insulin, food deprivation, translational regulation
- MeSH terms
- Administration, Oral, Animals, Food Deprivation, Insulin, Kinetics, Leucine, Phenylalanine, Proteins, Muscle, Skeletal, Rats
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