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Roles of KATP channels on the regulation of heat production and metabolism in adipose tissues

Research Project

Project/Area Number 19K06757
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionChiba University

Principal Investigator

LEE Eunyoung  千葉大学, 大学院医学研究院, 助教 (60583424)

Co-Investigator(Kenkyū-buntansha) 三木 隆司  千葉大学, 大学院医学研究院, 教授 (50302568)
波多野 亮  千葉大学, 大学院医学研究院, 助教 (60521713)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords脂肪組織 / 熱産生 / 脂肪酸代謝 / ATP感受性K+チャネル / 代謝恒常性 / KATPチャネル / 糖尿病 / 肥満 / エネルギー代謝
Outline of Research at the Start

肥満症は重要な代謝疾患であり、有効な治療法の確立が必要である。代謝センサーであるKATPチャネルの欠損マウス(KOマウス)では脂肪組織の糖取り込みが亢進し、高脂肪食下で肥満抵抗性を示す。そこでKOマウスのエネルギー代謝を解析したところ、寒冷不耐症で、寒冷時の褐色脂肪組織での遺伝子Xの発現誘導が消失していた(未発表)。また通常温度飼育下でも脂肪酸代謝酵素の発現が変化していた。そこで、本研究で脂肪組織での熱産生と脂質代謝調節におけるKATPチャネルの役割を解明する。

Outline of Final Research Achievements

KATP channel is a metabolic sensor that senses alteration in metabolism and regulates the electrical activity of various cell types. KATP channel-deficient mice (KO mice) exhibit the increased glucose uptake in the adipose tissues and obesity resistance against high fat diet. However, the role of KATP channel in the regulation of body temperature and lipid metabolism in adipose tissues remains unknown. In this study, we found that KO mice showed cold intolerance, and that cold exposure failed to induce mRNA expressions of the genes involved in fatty acid synthesis or modification (Elovl6 and Scd2) and a gene activated by parasympathetic nervous system (Pgc1a) in the brown adipose tissues of KO mice. In addition, the induction of these genes was also blunted in the brown adipose tissues of brain-specific KATP channel-deficient mice, indicating that KATP channel in the brain plays a significant role in controlling the metabolism in the brown adipose tissues under cold stress.

Academic Significance and Societal Importance of the Research Achievements

寒冷時の体温維持は生体の生命維持に必須な応答であり、健常人では寒冷環境下で脂肪組織の脂質代謝と熱産生が変化し、体温が維持される。KATPチャネルは様々な細胞の代謝センサーであるが、体温調節における役割は報告されていない。本研究の結果、KOマウスは寒冷不耐性を示し、脳のKATPチャネルが体温維持と脂質代謝制御に必須の分子であることが示された。体温制御の破綻は、エネルギー代謝疾患の発症とも密接に関係しており、KATPチャネルによる熱産生と脂肪代謝制御での役割解明は、糖尿病や肥満症などのエネルギー代謝疾患の病態の理解に有用であり、革新的治療薬の探索にも役立つ学術的な基盤となり得る。

Report

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

    (26 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (5 results) Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (3 results)

  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Nanjing University(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Nanjing University(中国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Cambridge University(英国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] GPR52 accelerates fatty acid biosynthesis in a ligand-dependent manner in hepatocytes and in response to excessive fat intake in mice2021

    • Author(s)
      Wada, M., Yukawa, K., Ogasawara, H. Suzawa, K., Maekawa, T., Yamamoto, Y., Ohta, T., Lee, E., Miki, T.
    • Journal Title

      iScience

      Volume: 24 Issue: 4 Pages: 102260-102260

    • DOI

      10.1016/j.isci.2021.102260

    • NAID

      120006997059

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lecithin Inclusion by α-Cyclodextrin Activates SREBP2 Signaling in the Gut and Ameliorates Postprandial Hyperglycemia2021

    • Author(s)
      Lee Eunyoung、Zhang Xilin、Noda Tomoe、Miyamoto Junki、Kimura Ikuo、Tanaka Tomoaki、Sakurai Kenichi、Hatano Ryo、Miki Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10796-10796

    • DOI

      10.3390/ijms221910796

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR-29 family.2021

    • Author(s)
      Li J, Zhang Y, Ye Y, Li D, Liu Y, Lee E, Zhang M, Dai X, Zhang X, Wang S, Zhang J, Jia W, Zen K, Vidal-Puig A, Jiang X, Zhang CY.
    • Journal Title

      J Extracell Vesicles.

      Volume: 10 Issue: 3

    • DOI

      10.1002/jev2.12055

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diet-Induced Obese Mice and Leptin-Deficient Lepob/ob Mice Exhibit Increased Circulating GIP Levels Produced by Different Mechanisms2019

    • Author(s)
      Lee Eunyoung、Miedzybrodzka Emily L.、Zhang Xilin、Hatano Ryo、Miyamoto Junki、Kimura Ikuo、Fujimoto Kosuke、Uematsu Satoshi、Rodriguez-Cuenca Sergio、Vidal-Puig Antonio、Gribble Fiona M.、Reimann Frank、Miki Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 18 Pages: 4448-4448

    • DOI

      10.3390/ijms20184448

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腸内細菌叢と宿主の代謝クロストーク(Metabolic crosstalk between gut microbiota and hosts)2022

    • Author(s)
      三木隆司、李恩瑛、芳川隼登、波多野亮、宮本潤基、木村郁夫
    • Organizer
      第99回日本生理学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 腎臓における糖代謝と糖新生の役割と制御2022

    • Author(s)
      波多野亮、李恩瑛、三木隆司
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膵β細胞傷害モデルマウスを用いた膵島再生機構の解析2021

    • Author(s)
      波多野亮, 張錫麟, 馬玉潔, 陳雪, 李恩瑛, 金田篤志, 三木 隆司
    • Organizer
      日本薬学会大会第141回年会
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Presentation] Adult murine pancreatic b cells retain repetitive proliferation capacity in a diphtheria toxin mediated β cell ablation model2021

    • Author(s)
      Xue Chen, Xilin Zhang, Ryo Hatano, Yujie Ma, Atsushi Kaneda, Eunyong Lee, Takashi Miki
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The effect of α-cyclodextrin on suppression of blood glucose via GLP-1 dependent and independent pathway.2021

    • Author(s)
      Lee E, Hatano R, Zhang X, Miyamoto J, Kimura I, Miki T.
    • Organizer
      EASD 2021 57th Annual Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of fatty acid biosynthesis in liver through GPR52 signaling.2021

    • Author(s)
      Mitsuo Wada, Kayo Yukawa, Hiroyuki Ogasawara, Koichi Suzawa, Tatsuya Maekawa, Yoshihisa Yamamoto, Takeshi Ohta, Eunyoung Lee, Takashi Miki.
    • Organizer
      第98回日本生理学会 the 98th Annual Meeting of The Physiological Society of Japan
    • Related Report
      2020 Research-status Report
  • [Presentation] Investigation of molecular mechanisms in pancreatic β cell regeneration using β-cell-specific injured mice2021

    • Author(s)
      Ryo Hatano, Xillin Zhang, Chen Xue, Eunyoung Lee, Atsushi Kaneda, Takashi Miki
    • Organizer
      第98回日本生理学会 the 98th Annual Meeting of The Physiological Society of Japan
    • Related Report
      2020 Research-status Report
  • [Presentation] レーザーマイクロダイセクション法による膵島再生の分子機構の解明2020

    • Author(s)
      張錫麟、波多野亮、李恩瑛、金田篤志、三木隆司
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 膵β細胞再生の分子機構2020

    • Author(s)
      三木隆司、波多野亮、張錫麟、陳雪、馬玉潔、金田篤志、李恩瑛
    • Organizer
      令和2年度生理研研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] エズリンの腎近位尿細管における膜タンパク質の局在制御と溶質再吸収調節機構2020

    • Author(s)
      波多野亮, 高山実樹子, 川口高徳, 福富俊之, 木村徹, 櫻井裕之, 李恩瑛, 三木隆司, 浅野真司
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Distinct mechanism for the elevation of plasma glucose-dependent insulinotropic polypeptide by high-fat-diet and by leptin-deficiency2019

    • Author(s)
      Eun-Young Lee, Xilin Zhang, Junki Miyamoto, Ikuo Kimura, Ryo Hatano, Takashi Miki
    • Organizer
      55th EASD Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肥満における高GIP血症の発症機序2019

    • Author(s)
      李恩瑛
    • Organizer
      第62回日本糖尿病学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脂肪組織の代謝シグナルによる糖調節機構2019

    • Author(s)
      李恩瑛、張錫麟、宮本潤基、木村郁夫、波多野亮、三木隆司
    • Organizer
      第62回日本糖尿病学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 腸管内の栄養素感知とインクレチン分泌制御2019

    • Author(s)
      三木隆司、李恩瑛、宮本潤基、木村郁夫
    • Organizer
      生体機能と創薬シンポジウム2019/日本薬学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Remarks] 千葉大学大学院医学研究院代謝生理学研究室ホームページ

    • URL

      https://www.m.chiba-u.ac.jp/class/physiol/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 千葉大学大学院 医学研究院 代謝生理学

    • URL

      http://www.m.chiba-u.ac.jp/class/physiol/index.html

    • Related Report
      2020 Research-status Report
  • [Remarks] 千葉大学大学院医学研究院代謝生理学 研究室ホームページ

    • URL

      http://www.m.chiba-u.ac.jp/class/physiol/index.html

    • Related Report
      2019 Research-status Report

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

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