Establishment of diagnostic marker and elucidation of fatty acid metabolism abnormality in autism by serum metabolome analysis

• Project/Area Number: 25461762
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: takagai shu 浜松医科大学, 子どものこころの発達研究センター, 准教授 (10447807)
• Co-Investigator(Kenkyū-buntansha): Matsuzaki Hideo 福井大学, 子どものこころの発達研究センター, 教授 (00334970) ; Tsuchiya Kenji 浜松医科大学, 子どものこころの発達研究センター, 准教授 (20362189)
• Co-Investigator(Renkei-kenkyūsha): Tsujii Masatsugu 中京大学, 現代社会学部, 教授 (20257546) ; Sugiyama Toshirou 浜松医科大学, 医学部, 教授 (60216348) ; Mashima Kazushi 大阪大学, 基礎工学研究科, 教授 (70159143)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自閉症 / メタボローム / 早期診断 / 脂質代謝

Outline of Final Research Achievements

In order to clarify the mechanism of VLDL down-regulation in autism spectrum disorder (ASD), we carried out measurements of free metabolite in plasma of children with ASD and examined correlation between VLDL triglyceride and the metabolites detected. By TOF-MS analysis, a total of 258 metabolites were detected in the serum of all set. Of these, 83 metabolites showed significantly different relative areas between the ASD children and the controls. The present study identified deviated serum 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 in the ASD participants. These results suggested that VLDL-specific lipolysis due to aberrant β-activation of fatty acid via oxidative stress and mitochondrial dysfunction may cause VLDL triglyceride decrease in serum of school-aged children with ASD.

Research Products

• [Journal Article] Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism. (2015)
  • Author(s): Maekawa M, Iwayama Y, Ohnishi T, Toyoshima M, Shimamoto C, Hisano Y, Toyota T, Balan S, Matsuzaki H, Iwata Y, Takagai S, Yamada K, Ota M, Fukuchi S, Okada Y, Akamatsu W, Tsujii M, Kojima N, Owada Y, Okano H, Mori N, Yoshikawa T
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 16239-16239
  • DOI: 10.1038/srep16239
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses. (2014)
  • Author(s): Maekawa M, Yamada K, Toyoshima M, Ohnishi T, Iwayama Y, Shimamoto C, Toyota T, Nozaki Y, Balan S, Matsuzaki H, Iwata Y, Suzuki K, Miyashita M, Kikuchi M, Kato M, Okada Y, Akamatsu W, Mori N, Owada Y, Itokawa M, Okano H, Yoshikawa T.
  • Journal Title: Biological Psychiatry Volume: 3223 Issue: 2 Pages: 00570-00578
  • DOI: 10.1016/j.biopsych.2014.07.025
  • NAID: 40020643113
  • Peer Reviewed / Open Access
• [Presentation] 脂質代謝特性に基づく自閉症予防法開発の試み (2014)
  • Author(s): 松﨑秀夫、東田陽博、森則夫
  • Organizer: 第55回日本児童青年精神医学会
  • Place of Presentation: 静岡県浜松市
  • Year and Date: 2014-10-13
  • Invited
• [Presentation] Specific Hypolipidemia Caused By VLDL Lipolysis in Children with ASD. (2014)
  • Author(s): Matsuzaki H, Iwata K, Nakamura K, Tsujii M and Mori N.
  • Organizer: 2014 International Meeting for Autism Research
  • Place of Presentation: アメリカ合衆国アトランタ市
  • Year and Date: 2014-05-17