Abstract
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 x g(-1) wet weight, respectively; in exercised VLCAD(-/-): 8.71 +/- 0.42, 9.03 +/- 0.93, and 14.82 +/- 1.20 nmol x 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.
Highlights
Long-chain acylcarnitines accumulate in longchain fatty acid oxidation defects, especially during periods of increased energy demand from fat
We were able to show for the first time that exercise stress, consisting of treadmill running, resulted in a significant, corresponding increase in C16:0, C18:1, and C18:2-carnitine and -CoA in VLCADϪ/Ϫ mouse muscle
Accumulation of long-chain acylcarnitines is well documented and has been implicated in the development of rhabdomyolysis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient patients [20]. It is unknown whether, and to what extent, this increase in long-chain acylcarnitines is mirrored by an increase in acyl-CoA esters of corresponding chain length
Summary
Long-chain acylcarnitines accumulate in longchain fatty acid oxidation defects, especially during periods of increased energy demand from fat. Corresponding increase in long-chain acyl-CoA and acylcarnitine after exercise in muscle from VLCAD mice. With the generation of a transgenic VLCAD-deficient mouse (VLCADϪ/Ϫ) that displays a stress-induced phenotype similar to that of humans [7, 8], new possibilities arise to study the effect of physiological stressors, such as fasting and exercise, at tissue level. In these mice it was shown that they have impaired Ca2+ handling [9] and heart rate dysfunction [10]. Similar to VLCADD-patients, the metabolic VLCADϪ/Ϫ mouse phenotype displays an accumulation of fat droplets [7] and long-chain acylcarnitines [11] in muscle
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
