• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Investigation of the effect of low carbohydrate ketogenic diet on tissue expression of epilepsy-related glycosphingolipids

Research Project

Project/Area Number 15H02907
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Eating habits
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Okuda Tetsuya  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (20443179)

Co-Investigator(Kenkyū-buntansha) 森田 直樹  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ付 (60371085)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywordsケトン食 / ガングリオシド / てんかん / GM2A / ST3GAL2 / 脂肪肝 / VLDLR / レプチン / ケトン産生食 / ローカーボダイエット / スフィンゴ糖脂質 / 糖質制限食 / 糖鎖マーカー / 糖鎖抗原 / 糖脂質 / 脳神経疾患 / 糖鎖 / 糖タンパク質
Outline of Final Research Achievements

Molecular targets associated with low-carbohydrate ketogenic diets (LCKDs) were explored using gene expression profiling in the liver of mice fed a LCKD. The result showed that the LCKD promoted the expression of glycosyltransferase genes involved in ganglioside synthesis and suppressed the expression of Gm2a, the gene encoding GM2 ganglioside activator protein, a lysosomal protein indispensable for ganglioside degradation. These changes were correlated with increased ganglioside content in the liver and serum. As gangliosides are mainly expressed in central nervous tissues, we also analyzed LCKD effect on cerebral cortex. Although ganglioside levels were unchanged in mice on the LCKD, Gm2a expression was significantly down-regulated. Further analyses suggested that the LCKD altered the expression levels of gangliosides in a limited area of central nervous system tissues susceptible to Gm2a.

Academic Significance and Societal Importance of the Research Achievements

てんかん患者の約3割は治療薬が奏効しないが、ケトン食はこのような難治性てんかんであっても改善できる。しかし、食べにくい、重度の便秘になるなど課題も多い。本研究によりケトン食の分子作用点が解明され、その作用を評価するための分子マーカーを開発できれば、その応用により患者に負担の少ないてんかん治療食の開発や創薬へとつながる点に社会的な意義がある。また、研究対象とするガングリオシドは様々な神経疾患の原因となるが、中枢神経組織における機能・役割は明確になっておらず、その解明につながる成果が期待できる点に学術的な意義がある。

Report

(5 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (40 results)

All 2020 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Peer Reviewed: 13 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (21 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] ポーランド科学アカデミー(ポーランド)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Dietary Control of Ganglioside Expression in Mammalian Tissues2020

    • Author(s)
      Okuda Tetsuya
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 1 Pages: 177-177

    • DOI

      10.3390/ijms21010177

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diet and Ganglioside Expression2020

    • Author(s)
      Okuda Tetsuya
    • Journal Title

      Encyclopedia

      Volume: v1 Pages: 513-513

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes2019

    • Author(s)
      Okuda Tetsuya
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 7627-7627

    • DOI

      10.1038/s41598-019-43952-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Data set for characterization of the glycosylation status of hepatic glycoproteins in mice fed a low-carbohydrate ketogenic diet2019

    • Author(s)
      Okuda Tetsuya
    • Journal Title

      Data in Brief

      Volume: 27 Pages: 104604-104604

    • DOI

      10.1016/j.dib.2019.104604

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A low-carbohydrate ketogenic diet induces the expression of very-low-density lipoprotein receptor in liver and affects its associated metabolic abnormalities2019

    • Author(s)
      Okuda Tetsuya
    • Journal Title

      npj Science of Food

      Volume: 3 Issue: 1 Pages: 25-25

    • DOI

      10.1038/s41538-019-0058-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of specific adaptive immune responses by immunization with newly designed artificial glycosphingolipids2019

    • Author(s)
      Okuda Tetsuya、Shimizu Kayoko、Hasaba Satoshi、Date Mutsuhiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 18803-18803

    • DOI

      10.1038/s41598-019-55088-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of anti-oligosaccharide IgG antibodies that recognize mammalian glycoproteins by immunization with novel artificial glycosphingolipids2019

    • Author(s)
      Okuda Tetsuya、Shimizu Kayoko、Hasaba Satoshi、Date Mutsuhiro
    • Journal Title

      Glycoconjugate Journal

      Volume: 36 Issue: 4 Pages: 356-356

    • DOI

      10.1007/s10719-019-09880-4

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Design of Carrier Molecules Suitable for Inducing Immunity to Oligosaccharide Antigens: Application to Anti-Glycoprotein Monoclonal Antibodies2018

    • Author(s)
      Testuya Okuda
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 30 Issue: 175 Pages: E113-E116

    • DOI

      10.4052/tigg.1762.1E

    • NAID

      130007419455

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2018-07-25
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design of Carrier Molecules Suitable for Inducing Immunity to Oligosaccharide Antigens: Application to Anti-Glycoprotein Monoclonal Antibodies2018

    • Author(s)
      奥田 徹哉
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 30 Issue: 175 Pages: J87-J90

    • DOI

      10.4052/tigg.1762.1J

    • NAID

      130007418664

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2018-07-25
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Data on immunoglobulin G antibodies induced by immunization of mice with globoside carrying very long-chain fatty acids2018

    • Author(s)
      Tetsuya Okuda
    • Journal Title

      Data in Brief

      Volume: 19 Pages: 256-260

    • DOI

      10.1016/j.dib.2018.05.014

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Data set for characterization of TNF-α inducible glycosphingolipids in vascular endothelial cells2018

    • Author(s)
      Tetsuya Okuda
    • Journal Title

      Data in Brief

      Volume: 21 Pages: 29-35

    • DOI

      10.1016/j.dib.2018.09.059

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of anti-oligosaccharide antibodies that recognize mammalian glycoproteins by immunization with a novel artificial glycosphingolipid2018

    • Author(s)
      Okuda Tetsuya、Fukui Asami
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 497 Issue: 4 Pages: 983-989

    • DOI

      10.1016/j.bbrc.2018.02.113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment2017

    • Author(s)
      Tetsuya Okuda
    • Journal Title

      Data in Brief

      Volume: 10 Pages: 449-453

    • DOI

      10.1016/j.dib.2016.12.001

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PUGNAc treatment provokes globotetraosylceramide accumulation in human umbilical vein endothelial cells2017

    • Author(s)
      Okuda Tetsuya
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 487 Issue: 1 Pages: 76-82

    • DOI

      10.1016/j.bbrc.2017.04.019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A very low carbohydrate ketogenic diet increases hepatic glycosphingolipids related to regulation of insulin signalling2016

    • Author(s)
      Tetsuya Okuda, Naoki Morita
    • Journal Title

      Journal of Functional Foods

      Volume: 21 Pages: 70-74

    • DOI

      10.1016/j.jff.2015.11.040

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 糖タンパク質の糖鎖構造をエピトープ認識するモノクローナル抗体の開発2019

    • Author(s)
      奥田 徹哉
    • Organizer
      第18回産総研・産技連LS-BT合同研究発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] スフィンゴ糖脂質の動態に着目したローカーボ・ケトン食の分子作用の研究2019

    • Author(s)
      奥田 徹哉
    • Organizer
      第18回産総研・産技連LS-BT合同研究発表会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] スフィンゴ糖脂質の糖鎖構造の制御による適応免疫の特異的誘導2019

    • Author(s)
      奥田 徹哉、狭場 諭、木戸脇 佳代子、伊達 睦廣
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] スフィンゴ糖脂質の糖鎖構造の制御による適応免疫の特異的誘導2019

    • Author(s)
      奥田 徹哉、狭場 諭、木戸脇 佳代子、伊達 睦廣
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] スフィンゴ糖脂質の糖鎖構造の制御による適応免疫の特異的誘導2019

    • Author(s)
      奥田 徹哉、狭場 諭、木戸脇 佳代子、伊達 睦廣
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Induction of anti-oligosaccharide IgG antibodies that recognize mammalian glycoproteins by immunization with novel artificial glycosphingolipids2019

    • Author(s)
      Okuda Tetsuya、Shimizu Kayoko、Hasaba Satoshi、Date Mutsuhiro
    • Organizer
      25th International Symposium on Glycoconjugate
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗てんかん食の摂取は関連遺伝子の転写制御を介してガングリオシドの発現を誘導する2019

    • Author(s)
      奥田 徹哉
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 超長鎖脂肪酸構造を特徴とする人工・天然糖脂質の免疫原性の解析と抗糖鎖モノクローナル抗体獲得への応用2018

    • Author(s)
      奥田 徹哉、狭場 諭、木戸脇 佳代子、伊達 睦廣
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低炭水化物ケトン産生食摂取マウスに見られるガングリオシド代謝関連遺伝子の発現変化2018

    • Author(s)
      奥田 徹哉
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] モノクローナル抗体の高効率獲得2018

    • Author(s)
      奥田 徹哉
    • Organizer
      テクノブリッジフェア2018 in つくば
    • Related Report
      2017 Annual Research Report
  • [Presentation] 超長鎖脂肪酸を含むスフィンゴ糖脂質類を用いた糖鎖認識抗体の開発2018

    • Author(s)
      奥田徹哉
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低炭水化物食摂取下の肥満マウス肝臓に見られる脂質代謝関連遺伝子の発現変化2017

    • Author(s)
      奥田徹哉
    • Organizer
      第16回 産総研・産技連LS-BT合同研究発表会
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Presentation] A very low carbohydrate ketogenic diet alters expression of lipid metabolism-related genes in ob/ob mouse liver2017

    • Author(s)
      奥田徹哉
    • Organizer
      日本農芸化学会2017年度大会
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Presentation] ケトン食摂取モデルマウスに見られるガングリオシドの発現増加とその分子基盤2017

    • Author(s)
      奥田徹哉
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2016 Annual Research Report
  • [Presentation] ケトン食摂取モデルマウスに見られる糖脂質代謝関連分子の発現増加とその分子基盤2017

    • Author(s)
      奥田徹哉
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] A very low carbohydrate ketogenic diet increases hepatic glycosphingolipids related to regulation of insulin signaling2016

    • Author(s)
      奥田徹哉、森田直樹
    • Organizer
      日本農芸化学会大会2016年度大会
    • Place of Presentation
      札幌コンベンションセンター、札幌市
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 持続的な低炭水化物食の摂取は肥満モデルマウス肝臓においてインスリン感受性関連糖脂質の発現量を増加させる2016

    • Author(s)
      奥田徹哉、森田直樹
    • Organizer
      第15回 産総研・産技連 LS-BT合同研究発表会
    • Place of Presentation
      産業技術総合研究所つくばセンター共用講堂 、つくば市
    • Year and Date
      2016-02-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] A very low carbohydrate ketogenic diet increases hepatic glycosphingolipids related to regulation of insulin signaling2016

    • Author(s)
      奥田徹哉
    • Organizer
      微生物研究の新展開
    • Place of Presentation
      秋葉原コンベンションホール、東京都
    • Year and Date
      2016-01-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] PUGNAc treatment promotes globoteetraosylceramide expression in vascular endothelial cell2016

    • Author(s)
      奥田徹哉
    • Organizer
      第35回日本糖質学会年会
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Presentation] PUGNAc処理後の血管内皮細胞に見られるGb4Cerの増加と関連酵素遺伝子の発現解析2016

    • Author(s)
      奥田徹哉
    • Organizer
      第89回日本生化学会大会
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Presentation] Alterations in liver glycosphingolipid content of mice fed a very low carbohydrate ketogenic diet2015

    • Author(s)
      奥田徹哉、森田直樹
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド、神戸市
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Remarks] モノクローナル抗体の高効率獲得

    • URL

      https://youtu.be/CxPNfs3or4c

    • Related Report
      2018 Annual Research Report
  • [Remarks] 疾患の要因となる”糖鎖”を認識する抗体を作るための化合物を開発

    • URL

      https://www.aist.go.jp/aist_j/new_research/2020/nr20200330/nr20200330.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 細胞・動物モデルを用いた、天然型糖脂質の機能解析と産業応用性の検証

    • URL

      https://unit.aist.go.jp/bpri/bpri-design/research.html

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2022-11-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi