Deficiency of
very-long-chain acyl-CoA dehydrogenase (
VLCAD) is the most common long-chain
fatty acid oxidation defect and presents with heterogeneous clinical manifestations. Accumulation of long-chain acylcarnitines and deficiency of free
carnitine have often been proposed to play an important role in disease pathogenesis. The
VLCAD-deficient mouse exhibits similar clinical and biochemical phenotypes to those observed in humans and, therefore, represents an excellent model to study
VLCAD deficiency. We measured
carnitine and
acylcarnitine profiles in liver, skeletal muscle (SkM), bile, and blood from
VLCAD knock-out mice and controls under nonstressed and various stress conditions.
Carnitine and acylcarnitines were extracted from body fluids with
methanol and from tissues with
acetonitrile, respectively, and were analyzed as their butyl
esters using electrospray ionization tandem mass spectrometry. Fasting combined with a cold challenge for 8 h significantly induced liver long-chain
acylcarnitine and free
carnitine production. Acylcarnitines in SkM predominantly accumulated during exercise with a concomitant decrease of free
carnitine. Changes in blood free
carnitine did not correlate with
carnitine homeostasis in liver and SkM. Our results demonstrate different tissue-specific long-chain
acylcarnitine profiles in response to various stressors, which may be of importance with respect to the heterogeneous clinical manifestations of
VLCAD deficiency in humans. Furthermore, we conclude that
carnitine biosynthesis in the liver seems sufficiently active to maintain liver
carnitine levels during increased demand. Our data suggest that
carnitine supplementation in long-chain beta-oxidation defects may not be required, and blood
carnitine concentrations do not reflect tissue
carnitine homeostasis.