Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion

Glover, Elisa I.; Phillips, Stuart M.; Oates, Bryan R.; Tang, Jason E.; Tarnopolsky, Mark A.; Selby, Anna; Smith, Kenneth; Rennie, Michael J.

doi:10.1113/jphysiol.2008.160333

Cited by 414Muscle metabolism and nutritionMuscle Physiology and DisordersNutrition and Health in Aging

Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion

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Glover, Elisa I., Phillips, Stuart M., Oates, Bryan R., Tang, Jason E., Tarnopolsky, Mark A., Selby, Anna, Smith, Kenneth, Rennie, Michael J.·2008·The Journal of Physiology

DOI 10.1113/jphysiol.2008.160333PMC PMC2655417

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Abstract

We tested the hypothesis that increasing blood amino acid (AA) availability would counter the physical inactivity‐induced reduction in muscle protein synthesis. We determined how 14 days of unilateral knee immobilization affected quadriceps myofibrillar protein synthesis (MPS) in young healthy subjects (10 men, 2 women, 21 ± 1 years; 80.2 ± 4.0 kg, mean ± s.e.m. ) in the post‐absorptive state and after infusing AA (10% Primene) at low or high doses (43 and 261 mg kg −1 h −1 ). Muscle cross‐sectional area (MRI) and peak isometric torque declined in the immobilized leg (−5.0 ± 1.2% and −25 ± 3%, respectively, both P < 0.005), but were unchanged (all P > 0.6) in the non‐immobilized leg. Immobilization induced a 27% decline in the rate of post‐absorptive MPS (immobilized, 0.027 ± 0.003: non‐immobilized, 0.037 ± 0.003% h −1 ; P < 0.001). Regardless of dose, AA infusion stimulated a greater rise in MPS in the non‐immobilized legs; at 4 h MPS was greater by +54 ± 12% with low dose and +68 ± 17% with high dose AA infusion (both P < 0.001). There was some evidence of delayed responsiveness of phosphorylation of Akt to high doses of AA and p70S6k at both doses but no marked differences in that of mTOR, GSK3β or eEF2. Phosphorylation of focal adhesion kinase (Tyr 576/577 ) was reduced ( P < 0.05) with immobilization. We observed no change in polyubiquitinated protein content after immobilization. We confirm that 14 days of immobilization reduces MPS in the post‐absorptive state and this diminution is reduced but not abolished by increased provision of AA, even at high rates. The immobilization‐induced decline in post‐absorptive MPS with the ‘anabolic resistance’ to amino acids can account for much of immobilization‐induced muscle atrophy.

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Authors: Glover, E. I., Phillips, S. M., Oates, B. R., Tang, J. E., Tarnopolsky, M. A., Selby, A., Smith, K., & Rennie, M. J.
Affiliations: McMaster University (CA)
University of Nottingham (GB)
ORCID: Phillips, Stuart M.
Tang, Jason E.
Tarnopolsky, Mark A.
Selby, Anna
Smith, Kenneth
Rennie, Michael J.
Venue: The Journal of Physiology
Publisher: Wiley
Published: 2008-12-12
Volume: 586
Issue: 24
Pages: 6049-6061
ISSN: 0022-3751 (ISSN-L)
1469-7793
DOI: 10.1113/jphysiol.2008.160333
PMC: PMC2655417
OpenAlex: W1573938781
Cited by: 414
References: 58
Citations by year: 2026: 15 · 2025: 14 · 2024: 15 · 2023: 22 · 2022: 18 · 2021: 21 · 2020: 25 · 2019: 36 · 2018: 23 · 2017: 17 · 2016: 26 · 2015: 38 · 2014: 28 · 2013: 28 · 2012: 31
FWCI: 8.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Physiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Biotechnology and Biological Sciences Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords: muscle protein synthesis, immobilization, anabolic resistance, amino acid infusion, knee immobilization, muscle atrophy, quadriceps, postabsorptive state, Akt phosphorylation, p70S6K, focal adhesion kinase, muscle cross-sectional area, isometric torque
MeSH terms: Glycogen Synthase Kinase 3 beta, Adult, Amino Acids, Amino Acids, Essential, Dose-Response Relationship, Drug, Female, Humans, Immobilization, Infusions, Intravenous, Insulin, Male, Muscle Proteins, Myofibrils, Phosphorylation, Protein Kinases, Glycogen Synthase Kinase 3, Ribosomal Protein S6 Kinases, 70-kDa, Proto-Oncogene Proteins c-akt, Focal Adhesion Protein-Tyrosine Kinases, Quadriceps Muscle, Muscle Strength, Elongation Factor 2 Kinase, Ubiquitination, Young Adult, TOR Serine-Threonine Kinases

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Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion

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