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Elucidation of a Novel Fat Depot with Potent Beiging after Cold Exposure

Research Project

Project/Area Number 17KK0188
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Eating habits
Research InstitutionChiba University

Principal Investigator

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

Project Period (FY) 2018 – 2020
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Keywords脂肪細胞 / 褐色化 / 組織幹細胞 / 分化 / 糖尿病 / 栄養学 / 生理学
Outline of Final Research Achievements

We identified a new white adipose depot with high beiging capacity after cold exposure that surpluses that in other white adipose tissue depots, as assessed by cold-induced gene expression of UCP1, a brown adipose tissue (BAT)-specific marker. Therefore, we coined as iBAT (inducible BAT). From our RNA-seq analysis, we found that the expressions of 35 genes (CIG1-35; cold-induced, iBAT- specific gene 1-35) were significantly increased in iBAT compared with inguinal WAT. Interestingly, CIG1, the most robustly increased gene, was found to be expressed in UCP1-positive cells in iBAT after cold exposure. In addition, we found that CIG1 expression was temporarily increased during differentiation of induced pluripotent stem cells (iPS) cells into brown adipocytes. These results suggest that CIG1 is suggested to be involved not only in early stage of adipocyte differentiation but also in beiging of iBAT under cold exposure.

Academic Significance and Societal Importance of the Research Achievements

今や全世界中で人口の多くが肥満を有しており、糖尿病、高血圧、動脈硬化など深刻な生活習慣病を引き起こす。しかし、脂肪エネルギーを熱に変換する褐色脂肪細胞を活性化することにより、肥満やインスリン抵抗性が改善することが知られており、これらの褐色脂肪細胞はヒト成人でも寒冷暴露により活性化することが報告されている。我々が発見した高効率の褐色化を示す新規脂肪組織での分子機序から遺伝子CIG1が脂肪細胞の分化や褐色化に重要であることが示されたことは学術的に意義が大きい。さらにもしCIG1を皮下脂肪細胞に発現誘導することにより、皮下脂肪の褐色化が誘導できれば新規の肥満治療戦略となる可能性がある。

Report

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

    (19 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Cambridge University(英国)2018

    • Related Report
      2020 Annual Research Report
  • [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
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
  • [Journal Article] Distinct roles of systemic and local actions of insulin on pancreatic β-cells.2018

    • Author(s)
      Kitamoto T, Sakurai K, Lee EY, Yokote K, Accili D, Miki T.
    • Journal Title

      Metabolism

      Volume: 81 Pages: 100-110

    • DOI

      10.1016/j.metabol.2017.12.017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gut carbohydrate inhibits GIP secretion via a microbiota/SCFA/FFAR3 pathway2018

    • Author(s)
      Lee Eun-Young、Zhang Xilin、Miyamoto Junki、Kimura Ikuo、Taknaka Tomoaki、Furusawa Kenichi、Jomori Takahito、Fujimoto Kosuke、Uematsu Satoshi、Miki Takashi
    • Journal Title

      Journal of Endocrinology

      Volume: 239 Issue: 3 Pages: 267-276

    • DOI

      10.1530/joe-18-0241

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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2021

    • 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 Annual Research Report
  • [Presentation] 膵β細胞再生の分子機構2021

    • 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 Annual Research Report
  • [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 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
      2020 Annual Research 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 Annual Research 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)
      6.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
  • [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
    • 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
  • [Presentation] Gut microbiome induced by intra-intestinal carbohydrates suppresses glucose-dependent insulinotropic polypeptide secretion.2018

    • Author(s)
      Lee, E.Y., Miyamoto, J., Kimura, I., Miki, T.
    • Organizer
      53rd EASD Annual Meeting, Berlin
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腸内細菌叢を介したGIP分泌抑制のメカニズム2018

    • Author(s)
      李恩瑛、張錫麟、宮本潤基、木村郁夫、三木隆司
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status 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 Annual Research Report

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Published: 2018-01-25   Modified: 2022-01-27  

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