title: Skeletal muscle molecular responses to resistance training and dietary supplementation in COPD.
abstract: BACKGROUND
  Skeletal muscle dysfunction is a systemic feature of chronic obstructive pulmonary disease (COPD), contributing to morbidity and mortality. Physical training improves muscle mass and function in COPD, but the molecular regulation therein is poorly understood.
  
  
  METHODS
  Candidate genes and proteins regulating muscle protein breakdown (ubiquitin proteasome pathway), muscle protein synthesis (phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway), myogenesis (MyoD, myogenin and myostatin) and transcription (FOXO1, FOXO3 and RUNX1) were determined in quadriceps muscle samples taken at four time points over 8 weeks of knee extensor resistance training (RT) in patients with COPD and healthy controls (HCs). Patients with COPD were randomly allocated to receive protein/carbohydrate or placebo supplements during RT.
  
  
  RESULTS
  59 patients with COPD (mean (SD) age 68.0 (9.3) years, forced expiratory volume in 1 s (FEV1) 46.9 (17.8) % predicted) and 21 HCs (66.1 (4.8) years, 105.0 (21.6) % predicted) were enrolled. RT increased lean mass (~5%) and strength (~20%) in all groups. Absolute work done during RT was lower throughout in patients with COPD compared with HCs. RT resulted in increases (from basal) in catabolic, anabolic, myogenic and transcription factor protein expression at 24 h, 4 weeks and 8 weeks of exercise in HCs. This response was blunted in patients with COPD, except for myogenic signalling, which was similar. Nutritional supplementation did not augment functional or molecular responses to RT.
  
  
  CONCLUSIONS
  The potential for muscle rehabilitation in response to RT is preserved in COPD. Except for markers of myogenesis, molecular responses to RT are not tightly coupled to lean mass gains but reflect the lower work done during RT, suggesting some caution when identifying molecular targets for intervention. Increasing post-exercise protein and carbohydrate intake is not a prerequisite for a normal training response in COPD.
authors.affiliation: MRC/ARUK Centre for Musculoskeletal Ageing Research, School of Biomedical Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Despina
authors.initials: D
authors.lastname: Constantin
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Menon
authors.forename: Linzy
authors.initials: L
authors.lastname: Houchen-Wolloff
authors.forename: Michael D
authors.initials: MD
authors.lastname: Morgan
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Singh
authors.forename: Paul
authors.initials: P
authors.lastname: Greenhaff
authors.forename: Michael C
authors.initials: MC
authors.lastname: Steiner
mesh_terms: D000368:Aged; D001706:Biopsy; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D019587:Dietary Supplements; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation*; D052097:Quadriceps Muscle / Q000378:metabolism* / Q000503:physiopathology; D055070:Resistance Training / Q000379:methods*
chemical_list: D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D009124:Muscle Proteins
keywords: COPD Mechanisms; Pulmonary Rehabilitation