Bed‐rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism

Shur, Natalie F.; Simpson, Elizabeth J.; Crossland, Hannah; Constantin, Despina; Cordon, Sally M.; Constantin-Teodosiu, Dumitru; Stephens, Francis B.; Brook, Matthew S.; Atherton, Philip J.; Smith, Kenneth; Wilkinson, Daniel J.; Mougin, Olivier E.; Bradley, Christopher; Macdonald, Ian A.; Greenhaff, Paul L.

Abstract

Background
Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown.

Methods
Ten healthy males (24 ± 1 years, body mass index 22.7 ± 0.6 kg/m2) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5 × 30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic–euglycaemic clamp (60 mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally.

Results
Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P < 0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P < 0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P < 0.05) and a 2.5% decrease in LMV (P < 0.01) during BR, along with a 30% decline in whole-body MPB after 2 days of BR (P < 0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ESR (P < 0.01 and P < 0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR.

Conclusions
Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

Citation

Shur, N. F., Simpson, E. J., Crossland, H., Constantin, D., Cordon, S. M., Constantin-Teodosiu, D., Stephens, F. B., Brook, M. S., Atherton, P. J., Smith, K., Wilkinson, D. J., Mougin, O. E., Bradley, C., Macdonald, I. A., & Greenhaff, P. L. (2024). Bed‐rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism. Journal of Cachexia, Sarcopenia and Muscle, 15(2), 603-614. https://doi.org/10.1002/jcsm.13431

• Journal Article Type: Article
• Acceptance Date: Dec 20, 2023
• Online Publication Date: Feb 12, 2024
• Publication Date: 2024-04
• Deposit Date: Jan 17, 2025
• Publicly Available Date: Jan 23, 2025
• Journal: Journal of Cachexia, Sarcopenia and Muscle
• Print ISSN: 2190-5991
• Electronic ISSN: 2190-6009
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 2
• Pages: 603-614
• DOI: https://doi.org/10.1002/jcsm.13431
• Public URL: https://nottingham-repository.worktribe.com/output/31452607
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13431