The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes
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BACKGROUND: The branched-chain amino acid (BCAA) leucine has been identified to be a key regulator of skeletal muscle anabolism. Activation of anabolic signalling occurs via the mammalian target of rapamycin (mTOR) through an undefined mechanism. System A and L solute carriers transport essential amino acids across plasma membranes; however it remains unknown whether an exogenous supply of leucine regulates their gene expression. The aim of the present study was to investigate the effects of acute and chronic leucine stimulation of anabolic signalling and specific amino acid transporters, using cultured primary human skeletal muscle cells. RESULTS: Human myotubes were treated with leucine, insulin or co-treated with leucine and insulin for 30 min, 3 h or 24 h. Activation of mTOR signalling kinases were examined, together with putative nutrient sensor human vacuolar protein sorting 34 (hVps34) and gene expression of selected amino acid transporters. Phosphorylation of mTOR and p70S6K was transiently increased following leucine exposure, independently to insulin. hVps34 protein expression was also significantly increased. However, genes encoding amino acid transporters were differentially regulated by insulin and not leucine. CONCLUSIONS: mTOR signalling is transiently activated by leucine within human myotubes independently of insulin stimulation. While this occurred in the absence of changes in gene expression of amino acid transporters, protein expression of hVps34 increased.
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Adequate protein intake, particularly leucine-rich sources, directly influences muscle hypertrophy by stimulating mTOR and MPS.
“Adequate protein intake, particularly of leucine-rich sources, directly influences muscle hypertrophy by stimulating mTOR and MPS.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [66]
In human skeletal muscle cells, leucine independently and transiently stimulated mTOR signaling without affecting amino acid transporter gene expression.
“The results showed that leucine independently and transiently stimulated mTOR signaling without affecting amino acid transporter gene expression.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [66]
Insulin increased mTOR signaling and modified gene expression of amino acid transporters in human myotubes.
“However, insulin also increased mTOR signaling and modified the gene expression of amino acid transporters.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [66]
Leucine enhanced expression of hVps34, which may regulate amino acid transport and mTOR activation in muscle tissue.
“Notably, leucine enhanced the expression of the nutrient-sensing protein hVps34, which may regulate amino acid transport and mTOR activation in muscle tissue [66].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [66]
Leucine increases NAD+ levels, mitochondrial biogenesis, insulin sensitivity, and lipid disposal in obese mice.
“Finally, leucine, which is sensed by mTOR247, increases NAD+ levels, mitochondrial biogenesis, insulin sensitivity and lipid disposal when given to obese mice248.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [247]
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- Authors
- Gran, P., & Cameron-Smith, D.
- Affiliations
- Deakin University (AU)
- Venue
- BMC Physiology
- Published
- 2011
- Volume
- 11
- Issue
- 1
- Pages
- 10
- ISSN
- 1472-6793 (ISSN-L)
- PMC
- PMC3141572
- OpenAlex
- W2004765914
- Cited by
- 95
- References
- 55
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 12 · 2019: 9 · 2018: 10 · 2017: 6 · 2016: 4 · 2015: 12 · 2014: 7 · 2013: 2 · 2012: 4
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- BMC Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Deakin University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- leucine, mTOR signaling, amino acid transporters, skeletal muscle anabolism, human myotubes, insulin, p70S6K, branched-chain amino acids, nutrient sensing, gene expression regulation
- MeSH terms
- Adult, Gene Expression Regulation, Humans, Insulin, Leucine, Male, Organ Culture Techniques, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, Muscle Fibers, Skeletal, Amino Acid Transport Systems, Ribosomal Protein S6 Kinases, 70-kDa, Eukaryotic Initiation Factor-4G, Prokaryotic Initiation Factor-3, Young Adult, Class III Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases
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