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.
Highlights
Chronic obstructive pulmonary disease (COPD) is a lung disease, and associates with several comorbidities
A trend toward increased lung compliance (+24%) was observed after 6 weeks of smoking in the vitamin D-deficient mice compared with vitamin D-deficient mice breathing air (P = 0.086, interaction term P < 0.05), while after 12 and 18 weeks, lung compliance was enhanced with smoking (P < 0.001), with no additional effect of vitamin D deficiency (Fig. 1A)
Vitamin D deficiency increased 4HNE with 33% (P < 0.001; Fig. 6C), but there was no interaction effect between smoking and vitamin D deficiency on 4HNE adduct formation. This is the first study examining the effects of vitamin D deficiency on skeletal muscle function in a smoking mouse model
Summary
Chronic obstructive pulmonary disease (COPD) is a lung disease, and associates with several comorbidities. Skeletal muscle dysfunction is of major concern, as it contributes, independently of lung function (Engelen et al 2000), to decreased functional capacity (Gosselink et al 1996), poor quality of life (Simpson et al 1992), increased health care utilization (Decramer et al 1997), and even mortality (Swallow et al 2007). Low serum levels of vitamin D are known to be associated with reduced muscle strength and performance, and lead to muscle atrophy, increased apoptosis, decreased protein synthesis, and perturbation in intracellular calcium homeostasis (Ceglia & Harris 2013).
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