VLDL-Specific Hypolipidemia Pattern in Human Subjects with Autism and Autistic Rodent Models

Background: The neurobiological basis for autism remains poorly understood, but evidence is mounting in support of lipid metabolism playing a role in autism.

Objectives: In order to clarify the role of lipids in autism, we examined serum lipid profiles of human subjects with autism and autistic rodent models.

Methods: This study enrolled 112 subjects with high-functioning autism recruited from the Asperger Society Japan and 106 age-matched healthy control subjects recruited by advertisement. All participants for both groups are Japanese male. In animal model experiment, valproic acid (VPA) exposed model mouse (Kolozsi et al 2009), human chromosome 15q11-13 duplication mouse (Nakatani et al 2009) and CD38 null mouse (Jin et al 2007) were tested as autistic rodent models. Fasting human blood samples were collected by venipuncture in a sitting position with a tourniquet from all participants between 8:00 and noon. Mice were anesthetized by diethyl ether and then its blood samples were collected from the left ventricle. All blood samples were kept at room temperature for 30 min and centrifuged at 2000g for 10 min in a refrigerated centrifuge. After that, they were divided into 200-µl of aliquots and stored at -80°C for subsequent analyses. The size distribution of serum lipoprotein particles was evaluated by high sensitivity lipoprotein profiling system with high-performance liquid chromatography (Skylight Biotech, Inc., Akita, Japan).

Results: The serum levels of total cholesterol and triacylglycerol in the infant subjects (under 20 years old) with high-functioning autism were significantly lower (Mann-Whitney U test: p < 0.001) than those of normal control subjects. In each fraction, there were significant differences in the serum levels of very-low density lipoprotein (VLDL) and high density lipoprotein (HDL) fraction. In particular, it's remarkable in VLDL fraction of triacylglycerol (p< 0.00003). However, there were no differences between the patients with autism and healthy subjects in serum chylomicron and low density lipoprotein (LDL) levels. In animal experiment, CD38 null mice in 4 weeks old have also shown serum lipid profile as above, but the other mice didn’t.

Conclusions: The association between autistic phenotype and abnormal serum lipid profile in human subjects and rodent models suggests that individuals with autism may be at increased risk for VLDL hypolipidemia in infancy and which might be implicated in the pathophysiology of autism.