Serum Acylglycerols Inversely Associate with Muscle Oxidative Capacity in Severe COPD
Year: 2020
Type: article
Study design: Observational Study
Abstract: PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with altered metabolism and body composition that accompany poor outcomes. We aimed to determine whether metabolic derangements in COPD are associated with skeletal muscle deconditioning and/or physical inactivity, independent of pulmonary obstruction. METHODS: We characterized serum metabolites associated with muscle oxidative capacity or physical activity in 44 COPD patients (forced expiratory volume in 1 s [FEV1] = 61% ± 4% predicted) and 63 current and former smokers with normal spirometry (CON) (FEV1 = 93% ± 2% predicted). Medial gastrocnemius oxidative capacity was assessed at rest from the recovery rate constant (k) of muscle oxygen consumption using near-infrared spectroscopy. Step counts and physical activity (average vector magnitude units [VMU] per minute) were measured over 5-7 d using triaxial accelerometry. Untargeted prime and lipid metabolites were measured using liquid chromatography and mass spectrometry. RESULTS: Muscle k (1.12 ± 0.05 vs 1.68 ± 0.06 min, P < 0.0001, d = 1.58) and VMU per minute (170 ± 26 vs 450 ± 50 VMU per minute, P = 0.004, d = 1.04) were lower in severe COPD (FEV1 < 50% predicted, n = 14-16) compared with CON (n = 56-60). A total of 129 prime metabolites and 470 lipids with known identity were quantified. Using sex as a covariate, lipidomics revealed 24 differentially expressed lipids (19 sphingomyelins) in COPD, consequent to a diminished sex difference of sphingomyelins in COPD (false discovery rate [FDR] < 0.05, n = 44). Total, and some individual, fatty acid concentrations were greater in severe COPD than CON (FDR < 0.05, n = 16, d = 0.56-1.02). After adjusting for FEV1% predicted, we observed that grouped diacylglycerides (ρ = -0.745, FDR = 0.03) and triacylglycerides (ρ = -0.811, FDR = 0.01) were negatively associated with muscle oxidative capacity, but not physical activity, in severe COPD (n = 14). CONCLUSION: Strong negative associations relate impaired mitochondrial function to the accumulation of serum aclyglycerides in severe COPD.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: National Science Foundation, U.S. Department of Veterans Affairs, American Thoracic Society, Shenzhen Technology University, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: G1545794908, G1681126986, MECHANISMS OF SKELETAL MUSCLE DYSFUNCTION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, UCLA Clinical and Translational Science Institute, (2 of 2) Genetic Epidemiology of COPD, (1 of 2) Genetic Epidemiology of COPD, MECHANISMS OF SKELETAL MUSCLE DYSFUNCTION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: RESTORING MITOCHONDRIAL FUNCTION BY HIGH-INTENSITY TRAINING, Shear stress and light-field to elucidate the initiation of cardiac outflow tract, Micro-Sensors to Study Electrical and Mechanical Coupling of Injured Myocardium, Determinants of 5 Year Progression of Muscle Dysfunction and Inactivity in COPDGene Participants., G9000296006, UCLA Clinical and Translational Science Institute
OpenAlex ID: W3045471526