Journal of Inherited Metabolic Disease

, Volume 33, Issue 3, pp 237–246 | Cite as

Pre-exercise medium-chain triglyceride application prevents acylcarnitine accumulation in skeletal muscle from very-long-chain acyl-CoA-dehydrogenase-deficient mice

  • Sonja Primassin
  • Sara Tucci
  • Diran Herebian
  • Annette Seibt
  • Lars Hoffmann
  • Frank ter Veld
  • Ute Spiekerkoetter
Original Article

Abstract

Dietary modification with medium-chain triglyceride (MCT) supplementation is one crucial way of treating children with long-chain fatty acid oxidation disorders. Recently, supplementation prior to exercise has been reported to prevent muscular pain and rhabdomyolysis. Systematic studies to determine when MCT supplementation is most beneficial have not yet been undertaken. We studied the effects of an MCT-based diet compared with MCT administration only prior to exercise in very-long-chain acyl-CoA dehydrogenase (VLCAD) knockout (KO) mice. VLCAD KO mice were fed an MCT-based diet in same amounts as normal mouse diet containing long-chain triglycerides (LCT) and were exercised on a treadmill. Mice fed a normal LCT diet received MCT only prior to exercise. Acylcarnitine concentration, free carnitine concentration, and acyl-coenzyme A (CoA) oxidation capacity in skeletal muscle as well as hepatic lipid accumulation were determined. Long-chain acylcarnitines significantly increased in VLCAD-deficient skeletal muscle with an MCT diet compared with an LCT diet with MCT bolus prior to exercise, whereas an MCT bolus treatment significantly decreased long-chain acylcarnitines after exercise compared with an LCT diet. C8-carnitine was significantly increased in skeletal muscle after MCT bolus treatment and exercise compared with LCT and long-term MCT treatment. Increased hepatic lipid accumulation was observed in long-term MCT-treated KO mice. MCT seems most beneficial when given in a single dose directly prior to exercise to prevent acylcarnitine accumulation. In contrast, continuous MCT treatment produces a higher skeletal muscle content of long-chain acylcarnitines after exercise and increases hepatic lipid storage in VLCAD KO mice.

Abbreviations

MCAD

Medium-chain acyl-CoA dehydrogenase

MCFA

Medium-chain fatty acids

MCT

Medium-chain triglycerides

KO

Knockout

LCAD

Long-chain acyl-CoA dehydrogenase

LCT

Long-chain triglycerides

VLCAD

Very-long-chain acyl-CoA dehydrogenase

WT

Wild type

Supplementary material

10545_2010_9105_Fig6_ESM.gif (517 kb)
Supplement 1

Palmitoyl-carnitine (A) and oleoyl-carnitine (B) concentrations in liver of wild-type (WT) (n = 5) and very-long-chain acyl-CoA dehydrogenase (VLCAD) knockout (KO) mice (n = 5). Acylcarnitine concentrations are presented in nmol/g wet weight of five differently treated groups. White bars and black bars represent WT and VLCAD KO mice, respectively. Values are means ± standard error of the mean (SEM). *P < 0.05 indicates significant differences between WT and VLCAD KO mice performed by Student’s t test; #p < 0.05 indicates significant differences between VLCAD KO mice in different groups performed by two-way analysis of variance (ANOVA). Samples were analyzed in duplicate. (GIF 517 kb)

10545_2010_9105_MOESM1_ESM.tif (2 mb)
High resolution image (TIFF 2003 kb)
10545_2010_9105_Fig7_ESM.gif (27 kb)
Supplement 2

Palmitoyl-carnitine (A) and oleoyl-carnitine (B) concentrations in blood of wild-type (WT) (n = 5) and very-long-chain acyl-CoA dehydrogenase (VLCAD) knockout (KO) mice (n = 5). Acylcarnitine concentrations are presented in µmol/L of five differently treated groups. White bars and black bars represent WT and VLCAD KO mice, respectively. Values are means ± standard error of the mean (SEM). *P < 0.05 indicates significant differences between WT and VLCAD KO mice performed by Student’s t test; # p < 0.05 indicates significant differences between VLCAD KO mice in different groups performed by two-way analysis of variance (ANOVA). Samples were analyzed in duplicate. (GIF 27 kb)

10545_2010_9105_MOESM2_ESM.tif (2.8 mb)
High resolution image (TIFF 2847 kb)

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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Sonja Primassin
    • 1
  • Sara Tucci
    • 1
  • Diran Herebian
    • 1
  • Annette Seibt
    • 1
  • Lars Hoffmann
    • 1
  • Frank ter Veld
    • 1
  • Ute Spiekerkoetter
    • 1
  1. 1.Department of General PediatricsUniversity Children’s HospitalDuesseldorfGermany

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