Skeletal Muscle Oxidative Metabolism in an Animal Model of Pulmonary Emphysema: Formoterol and Skeletal Muscle Dysfunction

Skeletal muscle dysfunction is a significant contributor to exercise limitation in pulmonary emphysema. Aim of this study was to investigate the skeletal muscle oxidative metabolism, before and following a long-acting beta agonist (LABA) aerosol exposure, such as formoterol, in pallid mouse (B6.Cg-Pldnpa/J), which has a deficiency in serum α1 antitrypsin (α1-PI) and develops spontaneous pulmonary emphysema. C57 BL/6J and its congener pallid mice of 8-12 and 16 months of age, were treated with vehicle or formoterol aerosol challenge for 120 seconds. Morphological and morphometrical studies, evaluations of mitochondrial ADP stimulated-respiration and of cytochrome oxidase activity on skeletal muscle, were performed. Moreover, mtDNA content in skeletal muscle and mediators linked to muscle mitochondrial function and biogenesis as well as TNF-α and PGC-1α were also evaluated. The lungs of pallid mice at 12 and 16 months of age showed patchy areas of air space enlargements with destruction of alveolar septa. No significantly differences were observed in basal values of mitochondrial skeletal muscle oxidative process between C57 BL/6J and pallid mice. LABA exposure significantly improved mitochondrial skeletal muscle oxidative processes in emphysematous mice, where the mtDNA content was significantly higher respect to 8 months-old pallid mice. This latter effect was compared to a significant increase of PGC-1α in skeletal muscles of 16 months-old pallid mice, with no significant changes in TNF-α levels. In conclusion, in emphysematous mice, that showed an increased mtDNA content, LABA inhaled exposure can improve mitochondria skeletal muscle oxidative process. The PGC-1α could be a possible mediator of this effect.