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Studies of the novel metabolic pathway down-regulating cholesterol biosynthesis in domestic cats

Research Project

Project/Area Number 17H03937
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Integrative animal science
Research InstitutionIwate University

Principal Investigator

Miyazaki Masao  岩手大学, 農学部, 准教授 (20392144)

Co-Investigator(Kenkyū-buntansha) 福田 智一  岩手大学, 理工学部, 教授 (40321640)
片山 泰章  岩手大学, 農学部, 准教授 (70436054)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsコレステロール / ネコ / メバロン酸経路 / 生合成 / コレステロール代謝 / フェリニン / 高コレステロール血症 / トランスジェニックマウス / 高脂血症 / 代謝 / 高脂肪食 / 動物 / 生理学 / 応用動物
Outline of Final Research Achievements

An excessive intake of lipid-rich diets may lead humans to hypercholesterolemia, a risk factor for cardiovascular disease. In contrast to humans, domestic cats, which evolved to strict carnivores, can consume such diets without increasing serum cholesterol levels. However little is known about the mechanism for preventing hypercholesterolemia in cats. Here, we report a specialized metabolic system enabling cats to minimize cholesterol biosynthesis. When dietary cholesterol intake is low, cats increase cholesterol biosynthesis, as do other mammals. In cholesterol-rich conditions, dimethylallyl diphosphate, a cholesterol precursor, is sidetracked from the cholesterol biosynthesis pathway. The precursor is finally excreted into the urine as non-proteinogenic amino acid felinine, a putative pheromone precursor, via the glutathione detoxification pathway.

Academic Significance and Societal Importance of the Research Achievements

本研究は新規性が非常に高い独創的な研究であり、完全肉食が可能なネコ科動物の脂質代謝の理解向上に大きく寄与するものである。比較生理学的な研究で、ヒトを含めた他の動物の病気克服などにも寄与すると考える。
高脂血症は動脈硬化の危険因子の一つでもある。スタチンは高脂血症の治療薬として最も普及している。しかし、一部の患者で薬効が不十分であることや、副作用の問題もあり、異なる作用機序を持つ新薬開発が現在も盛んに行われている。ネコが進化の過程で獲得した分岐経路亢進による高脂血症予防法を現代人が薬剤で獲得して治療に役立てるという我々の発想は極めて斬新であり、将来的に革新的な創薬展開に発展すると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] 尿や糞のにおいを介したネコの化学コミュニケーション2019

    • Author(s)
      宮崎雅雄
    • Journal Title

      香料

      Volume: 285 Pages: 49-56

    • NAID

      40022192010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 動物分泌物のにおいで獣害を防ぐ技術開発2019

    • Author(s)
      宮崎雅雄
    • Journal Title

      Aroma Research

      Volume: 78 Pages: 132-136

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Chemical Basis of Species, Sex, and Individual Recognition Using Feces in the Domestic Cat2018

    • Author(s)
      Masao Miyazaki, Tamako Miyazaki, Takashi Nishimura, Wataru Hojo, Tetsuro Yamashita
    • Journal Title

      Journal of chemical ecology

      Volume: 44 Issue: 4 Pages: 364-373

    • DOI

      10.1007/s10886-018-0951-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LC?MS/MS quantification of felinine metabolites in tissues, fluids, and excretions from the domestic cat ( Felis catus )2018

    • Author(s)
      Futsuta Ayami、Hojo Wataru、Miyazaki Tamako、Yamashita Tetsuro、Miyazaki Masao
    • Journal Title

      Journal of Chromatography B

      Volume: 1072 Pages: 94-99

    • DOI

      10.1016/j.jchromb.2017.11.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Olfactory discrimination of anal sac secretions in the domestic cat and the chemical profiles of the volatile compounds2017

    • Author(s)
      Miyazaki Tamako、Nishimura Takashi、Yamashita Tetsuro、Miyazaki Masao
    • Journal Title

      Journal of Ethology

      Volume: 36 Issue: 1 Pages: 99-105

    • DOI

      10.1007/s10164-017-0532-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potential use of domestic cat ( Felis catus ) urinary extracts for manipulating the behavior of free-roaming cats and wild small felids2017

    • Author(s)
      Miyazaki Masao、Nishimura Takashi、Hojo Wataru、Miyazaki Tamako、Laine Roger A.、Yamashita Tetsuro
    • Journal Title

      Applied Animal Behaviour Science

      Volume: 196 Pages: 52-60

    • DOI

      10.1016/j.applanim.2017.07.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Analysis of transgenic mice upregulating the felinine pathway for downregulating the cholesterol biosynthesis in cats2020

    • Author(s)
      Manon Miura, Rieko Katayama, Tetsuro Yamasita and Masao Miyazaki
    • Organizer
      International Symposium on Environmental Response Mechanisms in Plants and Animals
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コレステロール生合成経路を亢進させたネコ型マウスの表現型解析2019

    • Author(s)
      三浦舞音、片山理恵子、山下哲郎、宮崎雅雄
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ネコ腎臓に蓄積する脂肪滴の正体2019

    • Author(s)
      宮崎雅雄
    • Organizer
      第162回学術集会の開催について
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ネコの排泄物に種や性の情報を付加する嗅覚シグナルの同定とその生合成機構2019

    • Author(s)
      三浦舞音、山下哲郎、宮崎雅雄
    • Organizer
      第38回日本動物行動学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ネコ特異的なケミカルシグナルの生合成経路解明2018

    • Author(s)
      三浦 舞音、弗田 彩心、北条 渉、宮崎 珠子、山下 哲郎、宮崎 雅雄
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] コレステロール生合成を抑制するフェリニン経路に関与する遺伝子群の組織間発現解析2018

    • Author(s)
      三浦 舞音, 弗田 彩心, 山下 哲郎, 宮崎 雅雄
    • Organizer
      2018年度生化学会東北支部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Small felids decrease cholesterol biosynthesis by enhancing the shunt of the mevalonate pathway2017

    • Author(s)
      Miyazaki, M.
    • Organizer
      2nd International Symposium on Innovations in Plant and Food Sciences
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel lipid metabolism system developed in cats produces a species-specific chemosignal2017

    • Author(s)
      Miyazaki, M., Futsuta, A., Hojo, W., Miyazaki, T., and Yamashita, T.
    • Organizer
      2017 Meeting of the Chemical Signals in Vertebrates
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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