title: Delving into disability in Crohn's disease: dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease.
abstract: OBJECTIVE
  In Crohn's disease (CD), skeletal muscle mass and function are reduced compared to healthy controls, potentially resulting in disability. Mechanisms contributing to muscle impairment, and thus potential therapeutic targets, are poorly understood. This study aimed to measure and compare skeletal muscle size and molecular targets involved in skeletal muscle growth, in CD subjects and healthy controls.
  
  
  METHODS
  CD (n=27) and healthy (n=22) subjects were recruited from the IBD outpatient clinic and via local advertisement respectively. Demographics and clinical data were collected via survey and interview. Quadriceps muscle cross-sectional area was measured using peripheral quantitative CT scanning. Levels of muscle hypertrophy and atrophy signalling targets using quantitative PCR and western blotting were measured in muscle biopsies.
  
  
  RESULTS
  Muscle size was 14% lower (p=0.055) and a 54% lower phosphorylated:total (p:t) Akt ratio was measured in the muscle samples (p<0.05), indicating an attenuated muscle hypertrophy pathway in CD compared with controls. In those with CD, a lower p:t Akt ratio (<0.97) was associated with lower serum vitamin D3, lower physical activity indices (49 vs 64 mmol/L, 1.7 vs 2.2×10(6) accelerometer counts respectively, each p<0.05) and a trend towards lower serum ferritin levels (128 vs 322mg/L, p=0.07), compared with CD subjects with normal/high p:t Akt ratios.
  
  
  CONCLUSIONS
  The reduced muscle mass in CD may be explained, in part, by impaired activation of muscle protein synthesis pathways, notably the IGF1-Akt pathway. Normal vitamin D levels and regular exercise may be protective in CD against this trend, though confirmatory longitudinal studies are needed.
authors: Department of Gastroenterology & Hepatology, Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia. Electronic address: Daniel.van-Langenberg@monash.edu.
authors: D R
authors: DR
authors: van Langenberg
authors: Centre of Physical Activity and Nutrition (C-PAN) Research, School of Exercise and Nutrition Science, Deakin University, Burwood, Victoria, Australia.
authors: P
authors: P
authors: Della Gatta
authors: Centre of Physical Activity and Nutrition (C-PAN) Research, School of Exercise and Nutrition Science, Deakin University, Burwood, Victoria, Australia.
authors: B
authors: B
authors: Hill
authors: Centre of Physical Activity and Nutrition (C-PAN) Research, School of Exercise and Nutrition Science, Deakin University, Burwood, Victoria, Australia.
authors: E
authors: E
authors: Zacharewicz
authors: Department of Gastroenterology & Hepatology, Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia.
authors: P R
authors: PR
authors: Gibson
authors: Centre of Physical Activity and Nutrition (C-PAN) Research, School of Exercise and Nutrition Science, Deakin University, Burwood, Victoria, Australia.
authors: A P
authors: AP
authors: Russell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D001706:Biopsy; D018797:Cell Cycle Proteins; D002762:Cholecalciferol / Q000097:blood; D003424:Crohn Disease / Q000150:complications / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism*; D009929:Organ Size; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D052097:Quadriceps Muscle / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D015850:Interleukin-6; D010750:Phosphoproteins; D002762:Cholecalciferol; D007334:Insulin-Like Growth Factor I; D005293:Ferritins; D051057:Proto-Oncogene Proteins c-akt; D017027:Protein Tyrosine Phosphatases; C489397:UBASH3B protein, human
keywords: Disability; Inflammatory bowel disease; Muscle atrophy; Sarcopenia; Vitamin D