15889
Specific Hypolipidemia Caused By VLDL Lipolysis in Children with ASD
The neurobiological basis for autism remains poorly understood, but evidence is mounting in support of lipid metabolism playing a role in autism spectrum disorder (ASD). We have already revealed that Very Low Density Lipoprotein (VLDL) triglyceride was significantly decreased in children with ASD than those of normal control subjects (US PATENT #8518659). To elucidate the mechanism of VLDL down-regulation, it was necessary to clarify whether VLDL was reduced due to activation of the degradation or inhibition of its synthesis.
Objectives:
In order to clarify the mechanism of VLDL down-regulation in ASD, we carried out measurements of free metabolite in plasma of children with ASD and examined correlation between VLDL triglyceride and the metabolites detected.
Methods:
This study enrolled 30 children (6-11yrs old) with ASD recruited from the Asperger Society Japan and 30 age-matched healthy control subjects recruited by advertisement. Fasting human blood samples were collected by venipuncture in a sitting position with a tourniquet from all participants for both groups who are Japanese and drug-naïve. LC/CE-TOFMS measurement of free metabolite in the plasma was carried out using an Agilent LC System and CE Capillary Electrophoresis System (Agilent Technologies, Waldbronn, Germany). The size distribution of plasma lipoprotein particles was evaluated by high sensitivity lipoprotein profiling system with high-performance liquid chromatography (Skylight Biotech, Inc., Akita, Japan).
Results: By TOFMS analysis, a total of 258 metabolites were detected in the plasma of all set. Of these, 83 metabolites showed significantly different relative areas between the ASD children and the controls (p<0.05). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in children with ASD. More, we found significant correlation between VLDL triglyceride decrease and 20 metabolites change including 12 free fatty acids, 3 free acylcarnitines, alanine, loganin, 2-hydroxybutyric acid, 3-hydroxybutyric acid and O-acetylcarnitine (ALCAR) in the ASD participants (p<0.05). Of these 20 metabolites, Alanine and Loganin were lower but the others were higher in the ASD participants than controls.
Conclusions:
These results suggested that VLDL-specific lipolysis due to aberrant b-activation of fatty acid via oxidative stress and mitochondrial dysfunction may cause VLDL triglyceride decrease in plasma of children with ASD. VLDL triglyceride in peripheral blood might be surrogate marker implicated in oxidative stress and mitochondrial dysfunction in ASD.