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The role of calcitonin gene-related peptide (CGRP) in regulation of intestinal fat absorption

Research Project

Project/Area Number 19K07127
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionKitasato University

Principal Investigator

Hosono Kanako  北里大学, 医学部, 講師 (80532556)

Co-Investigator(Kenkyū-buntansha) 伊藤 義也  北里大学, 医学部, 准教授 (40203187)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords脂肪吸収 / 腸管リンパ管 / CGRP / RAMP1 / 肥満
Outline of Research at the Start

腸管リンパ管(乳糜管)は脂肪吸収という重要な役割を果たしている。従って、乳糜管の構造・機能異常は脂質循環障害をきたし肥満や脂質代謝異常などを発症する可能性がある。そこで、本研究では乳糜管を介した脂肪吸収に果たすCGRP/RAMP1の役割とその制御機構を解明し、腸管リンパ管の可塑性制御が肥満や代謝疾患治療につながるかを明らかにすることを目的とする。

Outline of Final Research Achievements

Lacteals, lymphatic vessels at the center of each intestinal villus, play an important role in fat absorption. The present study was examined whether CGRP (Calcitonin gene-related peptide) and its receptor, RAMP1 (receptor activity modifying protein 1), are involved in fat absorption via the lacteals. RAMP1 KO mice fed HFD for 8 weeks gained higher body weights compared with WT mice and developed severe obesity. In HFD fed RAMP1 KO mice, the structures of lacteals and the fat absorption function were compromised, suggesting that CGRP / RAMP1 is involved in the regulation of dietary fat absorption by lacteals.

Academic Significance and Societal Importance of the Research Achievements

これまで乳糜管における脂肪吸収のメカニズムは未解明であった。本研究では高脂肪食によって誘導された乳糜管可塑性にはCGRP/RAMP1が関与する可能性を検証するもので、知覚神経由来の神経ペプチドが肥満に関与するかどうかに焦点をあてて解明を進めるのが本研究の特徴である。脂肪吸収、脂肪循環の最初の関門である乳糜管機能にCGRP/RAMP1経路の役割を明らかにすることができれば、肥満・メタボリック症候群の発症への治療介入につながることが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Biologically active lipids in the regulation of lymphangiogenesis in disease states2022

    • Author(s)
      Majima Masataka、Hosono Kanako、Ito Yoshiya、Amano Hideki
    • Journal Title

      Pharmacology & Therapeutics

      Volume: 232 Pages: 108011-108011

    • DOI

      10.1016/j.pharmthera.2021.108011

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of Thromboxane Receptor Signaling in Enhancement of Lipopolysaccharide-Induced Lymphangiogenesis and Lymphatic Drainage Function in Diaphragm.2021

    • Author(s)
      Matsuda H, Ito Y, Hosono K, Tsuru S, Inoue T, Nakamoto S, Kurashige C, Hirashima M, Narumiya S, Okamoto H, Majima M.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 41 Issue: 4 Pages: 1390-1407

    • DOI

      10.1161/atvbaha.120.315507

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prostaglandin E receptor EP4 stimulates lymphangiogenesis to promote mucosal healing during DSS-induced colitis2020

    • Author(s)
      Hosono Kanako、Kojo Ken、Narumiya Shuh、Majima Masataka、Ito Yoshiya
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 128 Pages: 110264-110264

    • DOI

      10.1016/j.biopha.2020.110264

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lymphangiogenesis induced by vascular endothelial growth factor receptor 1 signaling contributes to the progression of endometriosis in mice2020

    • Author(s)
      Hattori Kyoko、Ito Yoshiya、Honda Masako、Sekiguchi Kazuki、Hosono Kanako、Shibuya Masabumi、Unno Nobuya、Majima Masataka
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 143 Issue: 4 Pages: 255-263

    • DOI

      10.1016/j.jphs.2020.05.003

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of receptor activity?modifying protein 1 suppresses the development of endometriosis and the formation of blood and lymphatic vessels2020

    • Author(s)
      Honda Masako、Ito Yoshiya、Hattori Kyoko、Hosono Kanako、Sekiguchi Kazuki、Tsujikawa Kazutake、Unno Nobuya、Majima Masataka
    • Journal Title

      Journal of Cellular and Molecular Medicine

      Volume: 24 Issue: 20 Pages: 11984-11997

    • DOI

      10.1111/jcmm.15823

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] RAMP1 signaling in immune cells regulates inflammation-associated lymphangiogenesis2020

    • Author(s)
      Tsuru Seri、Ito Yoshiya、Matsuda Hiromi、Hosono Kanako、Inoue Tomoyoshi、Nakamoto Shuji、Kurashige Chie、Mishima Toshiaki、Tsujikawa Kazutake、Okamoto Hirotsugu、Majima Masataka
    • Journal Title

      Laboratory Investigation

      Volume: - Issue: 5 Pages: 738-750

    • DOI

      10.1038/s41374-019-0364-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] RAMP1シグナルの脂肪肝内炎症抑制効果2021

    • Author(s)
      伊藤 義也、細野 加奈子 、後藤 卓也 、田邊 美奈、山下 敦 、長田 真由子 、畑中 公 、馬嶋 正隆 、 天野 英樹
    • Organizer
      第145回日本薬理学会関東部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マウス子宮内膜症におけるRAMP1の血管・リンパ管新生促進作用2020

    • Author(s)
      本田 雅子,伊藤 義也,服部 響子,細野加奈子,中本 修司,大高 史聖,津留 世里,馬嶋 正隆
    • Organizer
      第41回炎症再生医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Neuropeptide CGRP regulates inflammation by increasing lymphangiogenesis2020

    • Author(s)
      細野 加奈子、伊藤 義也、天野 英樹、馬嶋 正隆
    • Organizer
      第93回日本薬理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] TP signaling in immune cells promotes lymphangiogenesis in the diaphragm during peritonitis2020

    • Author(s)
      津留 世里、伊藤 義也、松田 弘美、細野 加奈子、岡本 浩嗣、馬嶋 正隆
    • Organizer
      第93回日本薬理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] RAMP1 signaling facilitates angiogenesis and lymphangiogenesis in the endometriotic lesions in mice2020

    • Author(s)
      本田 雅子、伊藤 義也、服部 響子、細野 加奈子、中本 修司、大高 史聖、津留 世里、馬嶋 正隆
    • Organizer
      第93回日本薬理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] リンパ管新生を制御する神経ペプチドCGRPの役割2019

    • Author(s)
      伊藤義也、津留世里、細野加奈子、天野英樹、馬嶋正隆
    • Organizer
      第43回日本リンパ学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 腹膜炎時の横隔膜リンパ管新生を制御する受容体活性調節蛋白1(RAMP1)の役割2019

    • Author(s)
      津留世里、伊藤義也、細野加奈子、井上智仁、松田弘美、藏重千絵、中本修司、大高史聖、岡本浩嗣、馬嶋正隆
    • Organizer
      第40回日本炎症再生医学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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