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Toward understanding a common molecular basis for deep torpor and fasting-induced torpor

Planned Research

Project AreaMammalian hibernation biology ~ survival strategies via hypometabolism and hypothermia
Project/Area Number 20H05766
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionHokkaido University

Principal Investigator

YAMAGUCHI Yoshifumi  北海道大学, 低温科学研究所, 教授 (10447443)

Co-Investigator(Kenkyū-buntansha) 渡邊 正知  福山大学, 薬学部, 准教授 (30306203)
Project Period (FY) 2020-10-02 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥39,780,000 (Direct Cost: ¥30,600,000、Indirect Cost: ¥9,180,000)
Fiscal Year 2022: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2021: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2020: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Keywords冬眠 / 哺乳類 / 生理学 / 体温調節 / 哺乳類の冬眠
Outline of Research at the Start

哺乳類の冬眠・休眠は、寒冷下で体熱産生を抑制した能動的低代謝状態で乗り切る生存戦略である。季節性に生じる冬眠では、長時間の低体温・不動状態の「深冬眠」とそこから自発的に復温する「中途覚醒」を幾度も繰り返す。しかし、その意義と制御機構は全く不明である。我々は小型冬眠動物シリアンハムスター(ハム)の深冬眠の際に大幅に発現変動する遺伝子群(DEGs)を、網羅的遺伝子発現解析から同定した。本研究では、我々が作成したDEG1欠損ハム及びDEG1欠損マウスを用いた代謝生理学的解析、分子生物学・生化学的解析等により冬眠・休眠制御におけるDEG1の機能を明らかにする。

Outline of Final Research Achievements

Hibernation in mammals is an adaptive strategy with hypometabolism and hypothermia in which thermogenesis is actively suppressed for the survival in seasons with cold and little food. Such extreme hypometabolism and hypothermia is called deep torpor and repeated during a long hibernation period. Mechanisms of hibernation and torpor remained largely unknown. Using molecular and genetic approaches, we found that the DEG1 gene, whose mRNA levels were high in multiple organs of the body during deep hibernation in the Syrian hamster, plays an important function in triggering hibernation.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、冬眠する哺乳類において冬眠発動に関わる遺伝子を遺伝学的手法で同定した初の事例として大きな学術的意義がある。更なる研究により、その制御機構が明らかになると期待される。また冬眠に関与する遺伝子の同定は、自然界の動物がいかにして厳しい冬季を生き抜くのかについての洞察を与え我々人間の視野を拡げる点だけでなく、将来的なヒトへの医療応用、たとえば臓器移植・救急医療・低体温療法などへの波及効果も期待される点で、社会的意義もあると言える。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (27 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 8 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] Yale university(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Yale University(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] How do cells of mammalian hibernators cope with cold stress?2023

    • Author(s)
      曽根正光、山口良文
    • Journal Title

      低温科学

      Volume: 81 Pages: 159-172

    • DOI

      10.14943/lowtemsci.81.159

    • ISSN
      1880-7593
    • Year and Date
      2023-03-20
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 冬眠する哺乳類と変温動物の低温適応機構2023

    • Author(s)
      山内 彩加林、山口 良文
    • Journal Title

      BIO Clinica

      Volume: 38(4)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Generation of transgenic mice expressing a FRET biosensor, SMART, that responds to necroptosis2022

    • Author(s)
      Murai Shin、Takakura Kanako、Sumiyama Kenta、Moriwaki Kenta、Terai Kenta、Komazawa-Sakon Sachiko、Seki Takao、Yamaguchi Yoshifumi、Mikami Tetuo、Araki Kimi、Ohmuraya Masaki、Matsuda Michiyuki、Nakano Hiroyasu
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 1331-1331

    • DOI

      10.1038/s42003-022-04300-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Step‐by‐step protocols for non‐viral derivation of transgene‐free induced pluripotent stem cells from somatic fibroblasts of multiple mammalian species2022

    • Author(s)
      Yoshimatsu Sho、Yamazaki Atsushi、Edamura Kazuya、Koushige Yuko、Shibuya Hisashi、Qian Emi、Sato Tsukika、Okahara Junko、Kishi Noriyuki、Noce Toshiaki、Yamaguchi Yoshifumi、Okano Hideyuki
    • Journal Title

      Development, Growth & Differentiation

      Volume: 64 Issue: 6 Pages: 325-341

    • DOI

      10.1111/dgd.12798

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 蛍光タンパク質レポーターを利用した細胞死イメージング2022

    • Author(s)
      山口良文
    • Journal Title

      医学のあゆみ

      Volume: 283(5) Pages: 23451-23454

    • Related Report
      2022 Annual Research Report
  • [Journal Article] 冬眠モデル哺乳類としてのゴールデンハムスター2022

    • Author(s)
      中川 哲, 山口 良文
    • Journal Title

      LABIO21

      Volume: 85 Pages: 5-8

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 冬眠する哺乳類に学ぶー代謝変化により飢餓・寒冷を乗り切る仕組み(前編)2022

    • Author(s)
      山口 良文
    • Journal Title

      臨床栄養

      Volume: 139(5) Pages: 628-632

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 冬眠する哺乳類に学ぶー代謝変化により飢餓・寒冷を乗り切る仕組み(後編)2022

    • Author(s)
      山口 良文
    • Journal Title

      臨床栄養

      Volume: 139(6) Pages: 748-752

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Hepatic resistance to cold ferroptosis in a mammalian hibernator Syrian hamster depends on effective storage of diet-derived α-tocopherol2021

    • Author(s)
      Anegawa Daisuke、Sugiura Yuki、Matsuoka Yuta、Sone Masamitsu、Shichiri Mototada、Otsuka Reo、Ishida Noriko、Yamada Ken-ichi、Suematsu Makoto、Miura Masayuki、Yamaguchi Yoshifumi
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 796-796

    • DOI

      10.1038/s42003-021-02297-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Caspase-3 regulates ureteric branching in mice via cell migration2021

    • Author(s)
      Awazu Midori、Yamaguchi Yoshifumi、Nagata Michio、Miura Masayuki、Hida Mariko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 559 Pages: 28-34

    • DOI

      10.1016/j.bbrc.2021.04.081

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] 冬眠に依存した体温概日リズムリセット機構の発見2023

    • Author(s)
      中川哲、山口良文
    • Organizer
      第17回日本生理学会プレコングレス
    • Related Report
      2022 Annual Research Report
  • [Presentation] Identification of hibernation-induced resetting of the circadian body temperature rhythm in Syrian golden hamster2023

    • Author(s)
      中川哲、山口良文
    • Organizer
      第100回日本生理学会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Autorecovery from hibernation period in Syrian hamsters involves a resetting of circadian body temperature rhythms2023

    • Author(s)
      Yoshifumi Yamaguchi
    • Organizer
      100th Aniversary Annual Meeting of the Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A food-storing facultative hibernator Syrian hamster as a model animal to comprehend the mysteries of mammalian hibernation from genetic and physiological aspect2022

    • Author(s)
      Yoshifumi Yamaguchi
    • Organizer
      Seminars at Wilhelminenberg Summer 2022, Vienna, Austria
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] モデル冬眠哺乳類シリアンハムスターから迫る哺乳類の冬眠を可能とする分子機構2022

    • Author(s)
      Yoshifumi Yamaguchi
    • Organizer
      日本生理学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 冬眠する哺乳類シリアンハムスターを用いた冬眠機構へのアプローチ2021

    • Author(s)
      山口良文
    • Organizer
      日本実験動物学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 冬眠動物が示す低温誘導性フェロプトーシス様細胞死への耐性2021

    • Author(s)
      山口良文
    • Organizer
      日本酸化ストレス学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 冬眠する哺乳類シリアンハムスターのフェロプトーシス様低温誘導性細胞死への耐性とそのビタミンE依存性2021

    • Author(s)
      山口良文
    • Organizer
      日本Cell Death学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Diet- and hibernation season- dependent enhancement of hepatic cold resistance in a mammalian hibernator Syrian hamster2021

    • Author(s)
      Yoshifumi Yamaguchi
    • Organizer
      Sapporo Symposium 2021
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 冬眠する哺乳類シリアンハムスターが冬眠時に示す骨格筋変化2021

    • Author(s)
      山口良文
    • Organizer
      日本体力医学学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] A mammalian hibernator Syrian hamster exhibits hepatic cold resistance with the aid of superior ability in retaining vitamin E2021

    • Author(s)
      Yoshifumi Yamaguchi
    • Organizer
      The 43th annual meeting of Molecular Biology Society of Japan
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Hibernator's hepatic cold resistance requires a diet-derived nutrient.2020

    • Author(s)
      Yamaguchi Y
    • Organizer
      nutrient. The 43rd Annual Meeting of the Molecular Biology Society of Japan, Kobe, Japan
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 冬眠する哺乳類が示す低温誘導性細胞死への耐性2020

    • Author(s)
      山口良文
    • Organizer
      第一回細胞死コロキアム
    • Related Report
      2020 Annual Research Report
  • [Book] 低温科学81巻「動物の寒冷適応戦略 生理生態と分子機構」2023

    • Author(s)
      低温科学研究所 編 (山口良文 他)
    • Total Pages
      205
    • Publisher
      低温科学研究所
    • Related Report
      2022 Annual Research Report
  • [Remarks] 冬眠哺乳類の低温耐性にビタミンEが関わることを発見~臓器移植・臓器保存への貢献に期待~

    • URL

      https://www.hokudai.ac.jp/news/2021/06/post-860.html

    • Related Report
      2021 Annual Research Report

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Published: 2020-10-30   Modified: 2024-01-30  

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