Corresponding increase in long-chain acyl-CoA and acylcarnitine after exercise in muscle from VLCAD mice

摘要

Long-chain acylcarnitines accumulate in long-chain fatty acid oxidation defects, especially during periods of increased energy demand from fat. To test whether this increase in long-chain acylcarnitines in very long-chain acyl-CoA dehydrogenase (VLCAD^−/−) knock-out mice correlates with acyl-CoA content, we subjected wild-type (WT) and VLCAD^−/− mice to forced treadmill running and analyzed muscle long-chain acyl-CoA and acylcarnitine with tandem mass spectrometry (MS/MS) in the same tissues. After exercise, long-chain acyl-CoA displayed a significant increase in muscle from VLCAD^−/− mice [C16:0-CoA, C18:2-CoA and C18:1-CoA in sedentary VLCAD^−/−: 5.95 ± 0.33, 4.48 ± 0.51, and 7.70 ± 0.30 nmol · g⁻¹ wet weight, respectively; in exercised VLCAD^−/−: 8.71 ± 0.42, 9.03 ± 0.93, and 14.82 ± 1.20 nmol · g⁻¹ wet weight, respectively (P < 0.05)]. Increase in acyl-CoA in VLCAD-deficient muscle was paralleled by a significant increase in the corresponding chain length acylcarnitine. Exercise resulted in significant lowering of the free carnitine pool in VLCAD^−/− muscle. This is the first study demonstrating that acylcarnitines and acyl-CoA directly correlate and concomitantly increase after exercise in VLCAD-deficient muscle.