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Changes in blood carnitine and acylcarnitine profiles of very long‐chain acyl‐CoA dehydrogenase‐deficient mice subjected to stress
Author(s) -
Spiekerkoetter U.,
Tokunaga C.,
Wendel U.,
Mayatepek E.,
Exil V.,
Duran M.,
Wijburg F. A.,
Wanders R. J. A.,
Strauss A. W.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01308.x
Subject(s) - carnitine , medicine , endocrinology , knockout mouse , dehydrogenase , chemistry , acetylcarnitine , biology , biochemistry , enzyme , receptor
Background In humans with deficiency of the very long‐chain acyl‐CoA dehydrogenase (VLCAD), C14–C18 acylcarnitines accumulate. In this paper we have used the VLCAD knockout mouse as a model to study changes in blood carnitine and acylcarnitine profiles under stress. Design VLCAD knockout mice exhibit stress‐induced hypoglycaemia and skeletal myopathy; symptoms resembling human VLCADD. To study the extent of biochemical derangement in response to different stressors, we determined blood carnitine and acylcarnitine profiles after exercise on a treadmill, fasting, or exposure to cold. Results Even in a nonstressed, well‐fed state, knockout mice presented twofold higher C14–C18 acylcarnitines and a lower free carnitine of 72% as compared to wild‐type littermates. After 1 h of intense exercise, the C14–C18 acylcarnitines in blood significantly increased, but free carnitine remained unchanged. After 8 h of fasting at 4 °C, the long‐chain acylcarnitines were elevated 5‐fold in knockout mice in comparison with concentrations in unstressed wild‐type mice ( P < 0·05), and four out of 12 knockout mice died. Free carnitine decreased to 44% as compared with unstressed wild‐type mice. An increase in C14–C18 acylcarnitines and a decrease of free carnitine were also observed in fasted heterozygous and wild‐type mice. Conclusions Long‐chain acylcarnitines in blood increase in knockout mice in response to different stressors and concentrations correlate with the clinical condition. A decrease in blood free carnitine in response to severe stress is observed in knockout mice but also in wild‐type littermates. Monitoring blood acylcarnitine profiles in response to different stressors may allow systematic analysis of therapeutic interventions in VLCAD knockout mice.