The combination of smoking with vitamin D deficiency impairs skeletal muscle fiber hypertrophy in response to overload in mice

Vitamin D deficiency, which is highly prevalent in the general population, exerts similar deleterious effects on skeletal muscles to those induced by cigarette smoking. We examined whether cigarette smoke (CS) exposure and/or vitamin D deficiency impairs the skeletal muscle hypertrophic response to overload. Male C57Bl/6JolaH mice on a normal or vitamin D-deficient diet were exposed to CS or room air for 18 weeks. Six weeks after initiation of CS or air exposure, sham surgery or denervation of the agonists of the left plantaris muscle was performed. The right leg served as internal control. Twelve weeks later, the hypertrophic response was assessed. CS exposure instigated loss of body and muscle mass, and increased lung inflammatory cell infiltration (p<0.05), independently of diet. Maximal exercise capacity, whole body strength, in situ plantaris muscle force and key markers of hypertrophic signaling (Akt, 4EBP1, FoxO1) were not significantly affected by smoking or diet. The increase in plantaris muscle fiber cross-sectional area in response to overload was attenuated in vitamin D-deficient CS-exposed mice (smoking x diet interaction for hypertrophy, p=0.03). In situ fatigue resistance was elevated in hypertrophied plantaris, irrespective of vitamin D deficiency and/or CS exposure. In conclusion, our data show that CS exposure or vitamin D deficiency alone did not attenuate the hypertrophic response of overloaded plantaris muscles, but this hypertrophic response was weakened when both conditions were combined. These data suggest that current smokers who also present with vitamin D deficiency may be less likely to respond to a training program.