title: Vitamin D deficiency impairs skeletal muscle function in a smoking mouse model.
abstract: Chronic obstructive pulmonary disease (COPD) is associated with skeletal muscle dysfunction. Vitamin D plays an important role in muscle strength and performance in healthy individuals. Vitamin D deficiency is highly prevalent in COPD, but its role in skeletal muscle dysfunction remains unclear. We examined the time-course effect of vitamin D deficiency on limb muscle function in mice with normal or deficient vitamin D serum levels exposed to air or cigarette smoke for 6, 12 or 18 weeks. The synergy of smoking and vitamin D deficiency increased lung inflammation and lung compliance from 6 weeks on with highest emphysema scores observed at 18 weeks. Smoking reduced body and muscle mass of the soleus and extensor digitorum longus (EDL), but did not affect contractility, despite type II atrophy. Vitamin D deficiency did not alter muscle mass but reduced muscle force over time, downregulated vitamin D receptor expression, and increased muscle lipid peroxidation but did not alter actin and myosin expression, fiber dimensions or twitch relaxation time. The combined effect of smoking and vitamin D deficiency did not further deteriorate muscle function but worsened soleus mass loss and EDL fiber atrophy at 18 weeks. We conclude that the synergy of smoking and vitamin D deficiency in contrast to its effect on lung disease, had different, independent but important noxious effects on skeletal muscles in a mouse model of mild COPD.
authors.affiliation: Laboratory of Respiratory DiseasesDepartment of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Cielen
authors.affiliation: Laboratory of Respiratory DiseasesDepartment of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Heulens
authors.affiliation: Laboratory of Respiratory DiseasesDepartment of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Maes
authors.affiliation: Laboratory of Clinical and Experimental EndocrinologyDepartment of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.affiliation: Laboratory of Clinical and Experimental EndocrinologyDepartment of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Laboratory of Respiratory DiseasesDepartment of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Janssens
authors.affiliation: Laboratory of Respiratory DiseasesDepartment of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium ghislaine.gayan-ramirez@med.kuleuven.be.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Gayan-Ramirez
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009218:Myosins / Q000378:metabolism; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D018167:Receptors, Calcitriol / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology / Q000503:physiopathology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000199:Actins; D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D009218:Myosins
keywords: COPD; cigarette smoke exposure; lung function; muscle atrophy; muscle function; oxidative stress