Early detection of skeletal muscle bioenergetic deficit by magnetic resonance spectroscopy in cigarette smoke-exposed mice

• Published in: PloS one Vol. 15; no. 6; p. e0234606
• Main Authors: Pérez-Rial, Sandra, Barreiro, Esther, Fernández-Aceñero, María Jesús, Fernández-Valle, María Encarnación, González-Mangado, Nicolás, Peces-Barba, Germán
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22-06-2020; Public Library of Science (PLoS)
• Subjects: Abnormalities; Adenosine triphosphate; Adenosine Triphosphate - biosynthesis; Adenosine Triphosphate - deficiency; Animals; ATP; Bioenergetics; Biology and Life Sciences; Biomedical research; Body weight; Body weight gain; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarettes; Complications and side effects; Cytochrome; Cytochrome-c oxidase; Cytochromes; Development and progression; Diagnosis; Disease; Emphysema; Energy Metabolism; Enzymatic activity; Enzyme activity; Enzymes; Exposure; Extremities; Gastrocnemius muscle; Health aspects; Homeostasis; Hypotheses; Laboratories; Lung diseases; Lung Diseases - diagnosis; Lungs; Magnetic resonance; Magnetic resonance spectroscopy; Magnetic Resonance Spectroscopy - methods; Medical research; Medicine and Health Sciences; Metabolism; Mice; Mitochondria; Mitochondria - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Muscles; Muscular diseases; Musculoskeletal system; Nicotiana - adverse effects; Nuclear magnetic resonance spectroscopy; Obstructive lung disease; Phosphorylation; Pulmonary Disease, Chronic Obstructive - diagnosis; Research parks; Resonance; Skeletal muscle; Smoke; Smoke - adverse effects; Smoking; Social Sciences; Spectroscopy; Spectrum analysis; Synthesis; Therapeutic applications; Spain
• DOI: 10.1371/journal.pone.0234606
• EISSN: 1932-6203

Skeletal muscle dysfunction is a common complication and an important prognostic factor in patients with chronic obstructive pulmonary disease (COPD). It is associated with intrinsic muscular abnormalities of the lower extremities, but it is not known whether there is an easy way to predict its presence. Using a mouse model of chronic cigarette smoke exposure, we tested the hypothesis that magnetic resonance spectroscopy allows us to detect muscle bioenergetic deficit in early stages of lung disease. We employed this technique to evaluate the synthesis rate of adenosine triphosphate (ATP) and characterize concomitant mitochondrial dynamics patterns in the gastrocnemius muscle of emphysematous mice. The fibers type composition and citrate synthase (CtS) and cytochrome c oxidase subunit IV (COX4) enzymatic activities were evaluated. We found that the rate of ATP synthesis was reduced in the distal skeletal muscle of mice exposed to cigarette smoke. Emphysematous mice showed a significant reduction in body weight gain, in the cross-sectional area of the total fiber and in the COX4 to CtS activity ratio, due to a significant increase in CtS activity of the gastrocnemius muscle. Taken together, these data support the hypothesis that in the early stage of lung disease, we can detect a decrease in ATP synthesis in skeletal muscle, partly caused by high oxidative mitochondrial enzyme activity. These findings may be relevant to predict the presence of skeletal bioenergetic deficit in the early stage of lung disease besides placing the mitochondria as a potential therapeutic target for the treatment of COPD comorbidities.