VLDL-specific increases of fatty acids in autism spectrum disorder correlate with social interaction

EBioMedicine

Kenji J. Tsuchiya¹  Shu Takagai²  Keiko Iwata³  Daisuke Kurita³  Masatsugu Tsujii³  Norio Mori⁴  Keisuke Wakusawa⁵  Takahiro Nara⁶  Taishi Miyachi⁷  Yosuke Kameno⁷  Toshiro Sugiyama⁸  Kiyokazu Takebayashi⁹  Tomoyasu Wakuda^1,10  Masato Maekawa^1,11  Takeo Yoshikawa^1,12  Motoko Maekawa^1,12  Tetsuo Ohnishi^1,12  Tomoko Toyota^1,12  Toru Fujioka^1,13  Yasuhide Iwata^1,13  Manabu Toyoshima^1,14  Hideo Matsuzaki^1,15  Takaharu Hirai^1,16  Kazuhiko Nakamura^1,17  Noriyoshi Usui^1,17  Kaori Matsumoto^1,17 

[1] Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka 541-8567, Japan;Center for Medical Research and Education, and Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka 565−0871, Japan;Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565−0871, Japan;Department of Community Health Nursing, School of Medical Sciences, University of Fukui, Fukui 910-1193, Japan;Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka 565−0871, Japan;Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565−0871, Japan;Life Science Innovation Center, University of Fukui, Fukui 910-1193, Japan;Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565−0871, Japan;Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan;Department of Pediatrics, Nagoya City University Medical School, Aichi 467-8601, Japan;Department of Psychiatry and Neurology, Fukude Nishi Hospital, Shizuoka 437-1216, Japan;Department of Psychiatry, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan;Department of Rehabilitation, Miyagi Children's Hospital, Miyagi 989-3126, Japan;Graduate School of Psychology, Kanazawa Institute of Technology, Ishikawa 921-8054, Japan;Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama 351−0198, Japan;Research Center for Child Mental Development, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan;Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan;

关键词: Autism spectrum disorder;    Lipid metabolism;    VLDL;    Social communication;    Polyunsaturated fatty acid;    Oxidative stress;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation. Methods: An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses. Findings: Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children. Interpretation: Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology. Funding: This study was supported mainly by MEXT, Japan.

【 授权许可】

Unknown