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Eatablishment and molecular mechanism of antiinflammatory action of vitamin C by using ODS rats.

Research Project

Project/Area Number 18H02155
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionNagoya University

Principal Investigator

Horio Fumihiko  名古屋大学, 生命農学研究科, 教授 (20165591)

Co-Investigator(Kenkyū-buntansha) 大野 民生  名古屋大学, 医学系研究科, 准教授 (90293620)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
KeywordsビタミンC / 抗炎症作用 / 炎症性サイトカイン / エンドトキシン / ODSラット
Outline of Final Research Achievements

In ODS rats unable to synthesize vitamin C (VC), we have demonstrated that VC deficiency elevates serum concentration of C-reactive protein (CRP) and stimulate hepatic CRP gene expression. As CRP is an inflammatory marker, VC deficiency causes inflammatory changes in liver. To examine the possibility that enterobacterium endotoxin incorporated into blood stream may stimulate hepatic CRP expression, we investigated in this study whether VC deficiency caused the stimulation of hepatic CRP expression or not in germ-free ODS rats. As a result, VC deficiency significantly provoked the stimulation of hepatic CRP expression in germ-free (endotoxin-free) ODS rats. Moreover, we clarified that VC deficiency induced the intestinal interleukin-6 production and suggested that interleukin-6 produced in the intestine stimulated the hepatic expression of CRP in VC deficiency.

Academic Significance and Societal Importance of the Research Achievements

VC欠乏による炎症性マーカーであるCRPの発現上昇と血中濃度上昇はODSラットとヒトとで共通したVCの生理作用であり、この現象が起こる機構において腸内細菌が介在しないことを本研究で初めて明らかにできた。本研究は無菌動物においてVCの生理機能を探求した国内外で初めての例であり、VCの生理機能の新たな側面を発掘し学術的意義は大きい。さらに、VC欠乏は腸管(空腸や回腸)に鋭敏に作用して炎症性サイトカインの産生を誘発することが初めて明らかとなり、腸管での炎症を抑えるためにはVCの十分な摂取が有効であるという社会的な波及効果がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (14 results)

All 2020 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (7 results)

  • [Journal Article] Ascorbic acid deficiency induces hepatic and intesitinal expression of inflammation-related genes irrespective of the presence or absence of gut microbiota in ODS rats.2020

    • Author(s)
      Kawade, N., Murai, A., Suzuki, W., Takeuchi, K., Kondo, M., Kobayashi, M. and Horio, F.
    • Journal Title

      J.Nutr.Biochem.

      Volume: 86 Pages: 108485-108485

    • DOI

      10.1016/j.jnutbio.2020.108485

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of Iah1, a candidate gene for diet-induced fatty liver, does not affect liver lipid accumulation in mice.2020

    • Author(s)
      Masuya, T., Suzuki, M., Tsujimura, J., Kanamori, S., Miyasaka, Y., Ohno, T., Murai, A., Horio, F. and Kobayashi, M.
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 5 Pages: e0233087-e0233087

    • DOI

      10.1371/journal.pone.0233087

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficiency of ascorbic acid decreases the contents of tetrahydrobiopterin in the liver and the brain of ODS rats.2020

    • Author(s)
      Takeshita, N., Kawade, N., Suzuki, W., Hara, S., Horio, F. and Ichinose, H.
    • Journal Title

      Neurosci Lett.

      Volume: 715 Pages: 134656-134656

    • DOI

      10.1016/j.neulet.2019.134656

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ascorbic acid deficiency increaseshepatic expression of acute phase proteins through the intestine-derived IL-6 and hepatic STST3 pathway in ODS rats.2019

    • Author(s)
      Kawade, N., Murai, A., Suzuki, W., Tokuda, Y., Kobayashi, M. and Horio, F.
    • Journal Title

      J.Nutr.Biochem.

      Volume: 70 Pages: 116-124

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アスコルビン酸欠乏は、腸管でのIL-6産生を上昇させて肝臓のSTAT3を活性化することにより急性期タンパク質の発現を上昇させる2019

    • Author(s)
      川出野絵、村井篤嗣、鈴木若奈、徳田優希、小林美里、堀尾文彦
    • Journal Title

      ビタミン

      Volume: 93 Pages: 485-487

    • NAID

      130007946242

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dietary Intake of Ascorbic Acid Attenuates Lipopolysaccharide-Induced Sepsis and Septic Inflammation in ODS Rat.2018

    • Author(s)
      Kawade, N., Tokuda, Y., Tsujino, S., Aoyama, H., Kobayashi, M., Murai, A. and Horio, H.
    • Journal Title

      J.Nutr.Sci.Vitaminol.

      Volume: 64 Pages: 404-411

    • NAID

      130007599146

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 糖・脂質代謝異常症の遺伝因子と食事因子に関する研究2018

    • Author(s)
      堀尾文彦
    • Journal Title

      日本栄養・食糧学会誌

      Volume: 71 Pages: 267-274

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 無菌ODSラットにおけるアスコルビン酸欠乏による腸管と肝臓での炎症様変化の解析2020

    • Author(s)
      川出野絵、村井篤嗣、鈴木若奈、竹内健三郎、小林美里、堀尾文彦
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
  • [Presentation] アスコルビン酸欠乏による肝臓でのサイトカイン発現の上昇2019

    • Author(s)
      川出野絵、鈴木若奈、小林美里、村井篤嗣、堀尾文彦
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アスコルビン酸欠乏による腸管での炎症様変化と肝臓での急性期タンパク質発現の上昇2019

    • Author(s)
      川出野絵、鈴木若奈、小林美里、村井篤嗣、堀尾文彦
    • Organizer
      日本ビタミン学会第71回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アスコルビン酸欠乏による腸管での網羅的な遺伝子発現変動の解析2019

    • Author(s)
      鈴木若奈、川出野絵、小林美里、村井篤嗣、堀尾文彦
    • Organizer
      日本ビタミン学会第71回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ビタミンCの末梢血単核球におけるLPS誘発性TNF-α産生抑制効果2018

    • Author(s)
      大谷祥也、川出野絵、鈴木若奈、辻野祥伍、小林美里、松田幹、村井篤嗣、堀尾文彦
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アスコルビン酸欠乏および不足による肝臓と腸管での炎症関連因子の発現誘導の解析2018

    • Author(s)
      川出野絵、鈴木若奈、大谷祥也、小林美里、村井篤嗣、堀尾文彦
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アスコルビン酸欠乏時の肝臓でのSTAT3活性化と腸管でのサイトカイン発現の上昇2018

    • Author(s)
      川出野絵、鈴木若奈、大谷祥也、小林美里、村井篤嗣、堀尾文彦
    • Organizer
      日本ビタミン学会第70回大会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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