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Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin
Open accessAbstract
Restriction of blood flow to a contracting muscle during low-intensity resistance exercise (BFR exercise) stimulates mTORC1 signaling and protein synthesis in human muscle within 3 h postexercise. However, there is a lack of mechanistic data to provide a direct link between mTORC1 activation and protein synthesis in human skeletal muscle following BFR exercise. Therefore, the primary purpose of this study was to determine whether mTORC1 signaling is necessary for stimulating muscle protein synthesis after BFR exercise. A secondary aim was to describe the 24-h time course response in muscle protein synthesis and breakdown following BFR exercise. Sixteen healthy young men were randomized to one of two groups. Both the control (CON) and rapamycin (RAP) groups completed BFR exercise; however, RAP was administered 16 mg of the mTOR inhibitor rapamycin 1 h prior to BFR exercise. BFR exercise consisted of four sets of leg extension exercise at 20% of 1 RM. Muscle biopsies were collected from the vastus lateralis before exercise and at 3, 6, and 24 h after BFR exercise. Mixed-muscle protein fractional synthetic rate increased by 42% at 3 h postexercise and 69% at 24 h postexercise in CON, whereas this increase was inhibited in the RAP group. Phosphorylation of mTOR (Ser(2448)) and S6K1 (Thr(389)) was also increased in CON but inhibited in RAP. Mixed-muscle protein breakdown was not significantly different across time or groups. We conclude that activation of mTORC1 signaling and protein synthesis in human muscle following BFR exercise is inhibited in the presence of rapamycin.
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“Human studies have since shown that phosphorylation of mTOR and its downstream substrates (i.e., p70s6k, 4EBP1) are critically involved in facilitating post-exercise increases in muscle protein synthesis (Drummond et al., 2009; Gundermann et al., 2014).”
From Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities (2021) · cites this paper as Gundermann et al., 2014
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Metadata
- Authors
- Gundermann, D. M., Walker, D. K., Reidy, P. T., Borack, M. S., Dickinson, J. M., Volpi, E., & Rasmussen, B. B.
- Affiliations
- Department of Nutrition and Metabolism,
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Rasmussen, Blake B.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2014-05-15
- Volume
- 306
- Issue
- 10
- Pages
- E1198-E1204
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC4116405
- OpenAlex
- W2140240000
- Cited by
- 143
- References
- 40
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 8 · 2023: 17 · 2022: 13 · 2021: 10 · 2020: 14 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 11 · 2015: 12 · 2014: 2
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute of Clinical and Translational Sciences
- National Institutes of Health
- National Institute on Aging (P30AG024832)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Child Health and Human Development
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Keywords
- blood flow restriction exercise, mTORC1 signaling, muscle protein synthesis, rapamycin, muscle protein degradation, skeletal muscle, S6K1 phosphorylation, mTOR phosphorylation, vastus lateralis, resistance training, leg extension
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Adolescent, Adult, Constriction, Humans, Male, Muscle Contraction, Regional Blood Flow, Protein Biosynthesis, Signal Transduction, Exercise, Muscle, Skeletal, Sirolimus, Multiprotein Complexes, Young Adult, TOR Serine-Threonine Kinases
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