Coordinated regulation of skeletal muscle mass and metabolic plasticity during recovery from disuse

Anita Kneppers, Pieter Leermakers, Nicholas Pansters, Evelien Backx, Harry Gosker, Luc van Loon, Annemie Schols, Ramon Langen, Lex Verdijk*

*Corresponding author for this work

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Abstract

Skeletal muscle regeneration after disuse is essential for muscle maintenance and involves the regulation of both mass- and metabolic plasticity-related processes. However, the relation between these processes during recovery from disuse remains unclear. In this study, we explored the potential interrelationship between the molecular regulation of muscle mass and oxidative metabolism during recovery from disuse. Molecular profiles were measured in biopsies from the vastus lateralis of healthy men after 1-leg cast immobilization and after 1 wk reloading, and in mouse gastrocnemius obtained before and after hindlimb suspension and during reloading (RL-1, -2, -3, -5, and -8 d). Cluster analysis of the human recovery response revealed correlations between myogenesis and autophagy markers in 2 clusters, which were distinguished by the presence of markers of early myogenesis, autophagosome formation, and mitochondrial turnover vs. markers of late myogenesis, autophagy initiation, and mitochondrial mass. In line with these findings, an early transient increase in B-cell lymphoma-2 interacting protein-3 and sequestosome-1 protein, and GABA type A receptor-associated protein like-1 protein and mRNA and a late increase in myomaker and myosin heavy chain-8 mRNA, microtubule-associated protein 1 light chain 3-II:I ratio, and FUN14 domain-containing-1 mRNA and protein were observed in mice. In summary, the regulatory profiles of protein, mitochondrial, and myonuclear turnover are correlated and temporally associated, suggesting a coordinated regulation of muscle mass- and oxidative metabolism-related processes during recovery from disuse.Kneppers, A., Leermakers, P., Pansters, N., Backx, E., Gosker, H., van Loon, L., Schols, A., Langen, R., Verdijk, L. Coordinated regulation of skeletal muscle mass and metabolic plasticity during recovery from disuse.

Original languageEnglish
Pages (from-to)1288-1298
Number of pages11
JournalFaseb Journal
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 2019

Keywords

  • remobilization
  • remodeling
  • protein turnover
  • myogenesis
  • mitophagy
  • SATELLITE CELL
  • MITOCHONDRIAL DYNAMICS
  • PGC-1-ALPHA OVEREXPRESSION
  • CREATINE SUPPLEMENTATION
  • LEG IMMOBILIZATION
  • GENE-EXPRESSION
  • FIBER SIZE
  • ATROPHY
  • REGENERATION
  • EXERCISE

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