title: Muscle inflammatory signaling in response to 9 days of physical inactivity in young men with low compared with normal birth weight.
abstract: OBJECTIVE
  The molecular mechanisms linking physical inactivity and muscle insulin resistance in humans have been suggested to include increased muscle inflammation, possibly associated with impaired oxidative metabolism. We employed a human bed rest study including 20 young males with normal birth weight (NBW) and 20 with low birth weight (LBW) and increased risk of diabetes.
  
  
  METHODS
  The subjects were studied before and after 9 days of bed rest using the euglycemic-hyperinsulinemic clamp and muscle biopsy excision. Muscle inflammatory status was assessed as nuclear factor-κB (NF-κB) activity and mRNA expression of the pro-inflammatory MCP1 (CCL2) and IL6 and the macrophage marker CD68. Furthermore, mRNA expression of genes central to oxidative phosphorylation (OXPHOS) was measured including ATP5O, COX7A1, NDUFB6, and UQCRB.
  
  
  RESULTS
  At baseline, muscle inflammatory status was similar in NBW and LBW individuals. After bed rest, CD68 expression was increased in LBW (P=0.03) but not in NBW individuals. Furthermore, expression levels of all OXPHOS genes were reduced after bed rest in LBW (P ≤ 0.05) but not in NBW subjects and were negatively correlated with CD68 expression in LBW subjects (P ≤ 0.03 for all correlations). MCP1 expression and NF-κB activity were unaffected by bed rest, and IL6 expression was too low for accurate measurements. None of the inflammatory markers correlated with insulin sensitivity.
  
  
  CONCLUSIONS
  Although LBW subjects exhibit disproportionately elevated CD68 mRNA expression suggesting macrophage infiltration and reduced OXPHOS gene expression when exposed to bed rest, our data altogether do not support the notion that bed rest-induced (9 days) insulin resistance is caused by increased muscle inflammation.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. martin.friedrichsen@ifi.ku.dk
authors.forename: Martin
authors.initials: M
authors.lastname: Friedrichsen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Ribel-Madsen
authors.forename: Brynjulf
authors.initials: B
authors.lastname: Mortensen
authors.forename: Christina N
authors.initials: CN
authors.lastname: Hansen
authors.forename: Amra C
authors.initials: AC
authors.lastname: Alibegovic
authors.forename: Lise
authors.initials: L
authors.lastname: Højbjerre
authors.forename: Mette P
authors.initials: MP
authors.lastname: Sonne
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
authors.forename: Bente
authors.initials: B
authors.lastname: Stallknecht
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV / Q000235:genetics; D015309:Glucose Clamp Technique; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D012146:Rest / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D018932:Chemokine CCL2; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV; D015850:Interleukin-6; D009247:NADH, NADPH Oxidoreductases; D016328:NF-kappa B; C111835:CCL2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C027208:ubiquinone-binding proteins; C513901:COX7A1 protein, human; C527690:NDUFB6 protein, human