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Developmental research of marine carotenoids on prevention of lifestyle-related diseases through their metabolite analysis and regulation of organ/cell interaction

Research Project

Project/Area Number 18H02274
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 40040:Aquatic life science-related
Research InstitutionHokkaido University

Principal Investigator

Hosokawa Masashi  北海道大学, 水産科学研究院, 教授 (10241374)

Co-Investigator(Kenkyū-buntansha) 岡松 優子  北海道大学, 獣医学研究院, 准教授 (90527178)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords海洋性カロテノイド / 生活習慣病予防 / アポカロテノイド / フコキサンチン / パラセントロン / 抗炎症作用 / アポー10’-フコキサンチナール / miRNA / β-カロテン開裂物 / アポアスタキサンチナール / 臓器・細胞間相互作用 / フコキサンチン開裂物 / 臓器間ネットワーク因子
Outline of Final Research Achievements

A fucoxanthin-derived apocarotenoid, paracentrone was identified in liver and white adipose tissue of mice fed fucoxanthin. Further, dietary fucoxanthin attenuated hepatic fat accumulation and inflammation in the diet-induced nonalcoholic steatohepatitis model mice. Paracentrone suppressed the overexpression of inflammatory factors in activated RAW264.7 macrophages. Further, apo-10′-fucoxanthinal with an epoxide residue also suppressed pro-inflammatory cytokines through regulating IkB phosphorylation, while beta-apo-8′-carotenal did not suppress inflammation. In adipocytes and hepatocytes, paracentrone and apo-10′-fucoxanthinal downregulated the mRNA expression of proinflammatory mediators induced by the culture medium of activated RAW264.7 cells. These results suggest that apo-fucoxanthinoids derived from fucoxanthin regulate organ/cell interaction involved in chronic inflammation, which is basis of the development of lifestyle-related diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究では、水産物に特徴的なカロテノイドの生活習慣病予防機構を明らかにするため、機能発現に関わる生体内代謝物の同定と抗炎症作用について検討した。ワカメなどの褐藻に含まれるフコキサンチンの新たな生体内代謝物としてパラセントロンを同定した。パラセントロンを含むフコキサンチン開裂物や代謝物は、活性化マクロファージや脂肪細胞、肝細胞に対して抗炎症作用を示し、生活習慣病の発症基盤となる慢性炎症に関わる細胞間相互作用を制御することを見出した。また、抗肥満作用や血糖値改善効果に加え、非アルコール性脂肪肝炎に対して予防効果が期待できることを示し、生活習慣病予防における水産物の有効性を示す成果を導いた。

Report

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

    (29 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 8 results)

  • [Journal Article] Seco-type β-Apocarotenoid Generated by β-Carotene Oxidation Exerts Anti-inflammatory Effects against Activated Macrophages2021

    • Author(s)
      Takatani Naoki、Beppu Fumiaki、Yamano Yumiko、Maoka Takashi、Hosokawa Masashi
    • Journal Title

      Journal of Oleo Science

      Volume: 70 Issue: 4 Pages: 549-558

    • DOI

      10.5650/jos.ess20329

    • NAID

      130008020860

    • ISSN
      1345-8957, 1347-3352
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice2020

    • Author(s)
      Takatani Naoki、Kono Yuka、Beppu Fumiaki、Okamatsu-Ogura Yuko、Yamano Yumiko、Miyashita Kazuo、Hosokawa Masashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 528 Issue: 2 Pages: 305-310

    • DOI

      10.1016/j.bbrc.2020.05.050

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Paracentrone in Fucoxanthin‐Fed Mice and Anti‐Inflammatory Effect against Lipopolysaccharide‐Stimulated Macrophages and Adipocytes2020

    • Author(s)
      Takatani Naoki、Taya Daisuke、Katsuki Ami、Beppu Fumiaki、Yamano Yumiko、Wada Akimori、Miyashita Kazuo、Hosokawa Masashi
    • Journal Title

      Molecular Nutrition & Food Research

      Volume: 65 Issue: 2 Pages: 2000405-2000405

    • DOI

      10.1002/mnfr.202000405

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] UCP1-dependent and UCP1-independent metabolic changes induced by acute cold exposure in brown adipose tissue of mice.2020

    • Author(s)
      Okamatsu-Ogura Y, Kuroda M, Tsutsumi R, Tsubota A, Saito M, Kimura K, Sakaue H.
    • Journal Title

      Metab Clin Exp

      Volume: 113 Pages: 154396-154396

    • DOI

      10.1016/j.metabol.2020.154396

    • NAID

      120007186809

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cold Exposure Increases Circulating miR-122 Levels via UCP1-Dependent Mechanism in Mice2020

    • Author(s)
      J.V. Bariuan, Y. Okamatsu-Ogura, A. Tsubota, S. Matsuoka, M. Saito, K. Kimura.
    • Journal Title

      Japanese Journal of Veterinary Research

      Volume: 68 Issue: 3 Pages: 187-195

    • DOI

      10.14943/jjvr.68.3.187

    • NAID

      120006887731

    • ISSN
      0047-1917
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 海洋性カロテノイドの健康機能性に関する最近の動向2020

    • Author(s)
      高谷直己・細川雅史
    • Journal Title

      日本食品安全協会会誌

      Volume: 15 Pages: 78-85

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 褐藻由来フコキサンチンの抗肥満効果2020

    • Author(s)
      細川雅史
    • Journal Title

      ファインケミカル

      Volume: 49(7) Pages: 22-27

    • Related Report
      2020 Annual Research Report
  • [Journal Article] フコキサンチンによる非アルコール性脂肪肝炎抑制効果2020

    • Author(s)
      高谷直己・細川雅史
    • Journal Title

      生物工学会誌

      Volume: 98 Pages: 529-532

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Association of circulating exosomal miR-122 levels with BAT activity in healthy humans2019

    • Author(s)
      Okamatsu-Ogura Yuko、Matsushita Mami、Bariuan Jussiaea Valente、Nagaya Kazuki、Tsubota Ayumi、Saito Masayuki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 13243-13243

    • DOI

      10.1038/s41598-019-49754-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired adrenergic agonist-dependent beige adipocyte induction in obese mice2019

    • Author(s)
      Shin W, Okamatsu-Ogura Y, Matsuoka S, Tsubota A, Kimura K.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 81 Issue: 6 Pages: 799-807

    • DOI

      10.1292/jvms.19-0070

    • NAID

      130007660444

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] マウス褐色脂肪組織において寒冷刺激により誘導されるUCP1依存的および非依存的代謝変化2021

    • Author(s)
      岡松 優子・黒田雅士・堤理恵・坪田あゆみ・斉藤昌之・木村和弘・阪上浩
    • Organizer
      第41回日本肥満学会・第38回日本肥満症治療学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 非アルコール性脂肪肝炎誘導モデルマウスに対する海洋性カロテノイドfucoxanthinの炎症抑制作用2020

    • Author(s)
      高谷直己・河野友香・別府史章・宮下和夫・細川雅史
    • Organizer
      第74回日本栄養・食糧学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] β-Carotene由来アポカロテノイドによる炎症抑制機構2020

    • Author(s)
      高谷直己・別府史章・山野由美子・ 沖津貴志・眞岡孝至・細川雅史
    • Organizer
      第59回日本油化学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 寒冷暴露は褐色脂肪の熱産生タンパク質UCP1依存的に血中miR-122を上昇させる2020

    • Author(s)
      Bariuan Jussiaea・岡松 優子・松岡 慎也・坪田 あゆみ・斉藤 昌之・木村 和弘
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 海洋性カロテノイド開裂物(アポカロテノイド)の機能性2020

    • Author(s)
      細川雅史
    • Organizer
      2019年度第1回脂質駆動学術産業創生研究部会講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Bio-functions of Marine Chemical “Fucoxanthin” in Brown Seaweeds2019

    • Author(s)
      M. Hosokawa
    • Organizer
      The 4th EMBRIO International Symposium 2019 and The 7th International Symposium of East Asia Fisheries Technologist Association (EAFTA)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 海藻成分の特徴と健康機能2019

    • Author(s)
      細川雅史
    • Organizer
      日本食品科学工学会第66回大会 シンポジウム「食資源としての海藻を科学する」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 持続可能な海藻資源の活用、生産・加工の連携、食形態と栄養・機能性2019

    • Author(s)
      細川雅史
    • Organizer
      第28回 医食農連携プラットフォーム研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 海洋性カロテノイドfucoxanthinの新規生体内開裂物による炎症抑制機構2019

    • Author(s)
      高谷直己・田谷大輔・宮下和夫・細川雅史
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アポフコキサンチノイドによる炎症抑制機構解析2019

    • Author(s)
      高谷直己・別府史章・沖津貴志・山野由美子・和田昭盛・宮下和夫・細川雅史
    • Organizer
      第33回カロテノイド研究談話会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] アスタキサンチン由来アポカロテノイドによる炎症抑制機構2019

    • Author(s)
      高谷直己・別府史章・宮下和夫・細川雅史
    • Organizer
      日本油化学会第58回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] フコキサンチンのUCP1欠損マウスにおける ミトコンドリア因子の発現誘導2019

    • Author(s)
      秋田知輝・岡松優子・別府史章 ・宮下和夫・ 細川雅史
    • Organizer
      日本油化学会第58回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 授乳期の高脂肪食給餌は、腸内細菌叢への影響を介して仔マウスにおけるベージュ脂肪細胞の発生を抑制する2019

    • Author(s)
      岡松優子・土生優妃・高橋菜摘・坪田あゆみ・園山慶・長屋一輝・木村和弘
    • Organizer
      第24回アディポサイエンス・シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] エネルギー代謝における褐色脂肪組織の役割と制御機構の解明2019

    • Author(s)
      岡松優子
    • Organizer
      第40回日本肥満学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] UCP1欠損マウスに対するフコキサンチンの抗肥満作用特性2019

    • Author(s)
      秋田知輝・岡松優子・宮下和夫・細川雅史
    • Organizer
      平成31年度日本水産学会春季大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Bio-functions and biotechnology of marine algal lipids2018

    • Author(s)
      M. Hosokawa
    • Organizer
      JOCS-AOCS Joint Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] フコキサンチンのエネルギー代謝制御機能2018

    • Author(s)
      大内裕佳・秋田知輝・立山莉帆・岡松優子・宮下和夫・細川雅史
    • Organizer
      第20回マリンバイオテクノロジー学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Anti-inflammatory effects of apo-fucoxanthinoids2018

    • Author(s)
      M. Hosokawa
    • Organizer
      14th International Symposium on Biocatalysis and Agricultural Biotechnology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] White adipocytes suppress brown adipocyte differentiation by secreting factors during the postnatal development of BAT in hamsters2018

    • Author(s)
      Y. Okamatsu-Ogura, K. Nagaya, J. Mae, A. Tsubota, K. Kimura
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report

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

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