Serum Acylglycerols Inversely Associate with Muscle Oxidative Capacity in Severe COPD

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 [FEV(1)] = 61% ± 4% predicted) and 63 current and former smokers with normal spirometry (CON) (FEV(1) = 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(−1), 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 (FEV(1) < 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 FEV(1)% 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.