Interaction between Physical Activity and Smoking on Lung, Muscle, and Bone in Mice

Abstract

Physical inactivity is an important contributor to skeletal muscle weakness, osteoporosis and weight loss in chronic obstructive pulmonary disease. However, the effects of physical inactivity, in interaction with smoking, on lung, muscle and bone are poorly understood. To address this issue, male mice were randomly assigned into an active (daily running), moderately inactive (space restriction) or extremely inactive group (space restriction followed by hindlimb suspension to mimic bed rest) during 24 weeks and simultaneously exposed to either cigarette smoke or room air. The effects of different physical activity levels and smoking status and their respective interaction were examined on lung function, body composition, in vitro limb muscle function and bone parameters. Smoking caused emphysema, reduced food intake with subsequent loss of body weight, fat, lean and muscle mass but increased trabecular bone volume. Smoking induced muscle fiber atrophy which did not result in force impairment. Moderate inactivity only affected lung volumes and compliance, whereas extreme inactivity increased lung inflammation, lowered body and fat mass, induced fiber atrophy with soleus muscle dysfunction and reduced exercise capacity and all bone parameters. When combined with smoking, extreme inactivity also aggravated lung inflammation and emphysema, and accelerated body and muscle weight loss. This study shows that extreme inactivity, especially when imposed by absolute rest, accelerates lung damage and inflammation. When combined with smoking, extreme inactivity is deleterious for muscle bulk, bone and lungs. These data highlight that the consequences of physical inactivity during the course of COPD should not be neglected.

Impaired calcium signaling in muscle fibers from intercostal and foot skeletal muscle in a cigarette smoke-induced mouse model of COPD

“…Importantly, this mouse model is a valuable tool for further examination of the role of smoking in the systemic pathogenesis in COPD, such as respiratory [62][63][64] and skeletal muscle atrophy and dysfunction. [31][32][33] In conclusion, in this report, we demonstrate the effects of chronic cigarette exposure on actionpotential induced Ca 21 transients in intercostal and intrinsic foot muscles. The intrinsic muscles of the foot are important for ambulation and balance in bipeds and quadrupeds, including humans and small mammals.…”

“…Nevertheless, whole‐body cigarette smoke exposure has been previously demonstrated to produce emphysematous mice, with alveolar destruction and airspace enlargement, the hallmarks of emphysema. Importantly, this mouse model is a valuable tool for further examination of the role of smoking in the systemic pathogenesis in COPD, such as respiratory and skeletal muscle atrophy and dysfunction …”

“…Muscle tissues were isolated from control and 6 month whole‐body cigarette smoke‐exposed mice. This 6‐month whole‐body cigarette smoke exposure is known to cause muscle dysfunction in different species, including mice . The procedures for isolating single muscle fibers were previously described in detail .…”

“…This 6-month wholebody cigarette smoke exposure is known to cause muscle dysfunction in different species, including mice. [31][32][33] The procedures for isolating single muscle fibers were previously described in detail. 34 In brief, intercostal (combined internal and external) and FDB muscles were dissected and enzymatically digested, then mechanically triturated with a polished glass pipette.…”

Two Weeks of Smoking Cessation Reverse Cigarette Smoke-Induced Skeletal Muscle Atrophy and Mitochondrial Dysfunction in Mice

“…The exercise test consisted in a 5-minute warm up on a treadmill (0% incline, 3 m/min), and the speed was increased by 1 m/min every minute until exhaustion. Maximal exercise capacity was defined as the maximum speed 26 . Latency-to-fall time was measured after placing the mice on a grid that was subsequently inverted and served as a surrogate marker for maximal muscle strength 26 .…”