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Establishment of strategies for anti-obesity and improvement of glucose and lipid metabolism through clarifying physiological significance of SHBG

Research Project

Project/Area Number 17K16158
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionThe University of Tokyo

Principal Investigator

Yamazaki Hiroki  東京大学, 医科学研究所, 助教 (60784337)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords抗肥満 / 抗炎症 / 脂質代謝 / 慢性炎症 / 臓器連関 / エネルギー代謝 / 糖・脂質代謝 / 性ホルモン結合グロブリン(SHBG)
Outline of Final Research Achievements

Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for diabetes and metabolic syndrome. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, we focused on the effects of SHBG on inflammation and lipid metabolism in vitro. Incubation with SHBG suppressed lipopolysaccharide-induced inflammatory cytokines in adipocytes and macrophages. In addition, SHBG treatment induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene levels. These effects of SHBG were not robustly altered by coaddition of large amounts of testosterone or estradiol, although slight modifications were observed. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is against the incidence of metabolic syndrome.

Academic Significance and Societal Importance of the Research Achievements

肥満では、脂肪組織における脂肪細胞の肥大や慢性炎症を素地として、全身性の種々の代謝異常が惹起される。本研究では、SHBGがかかる病態に抑制的に作用する可能性を示した。このようなSHBGの生理活性がどのように発揮されるか、その詳細の解明は、糖尿病やメタボリックシンドロームに対する新たな予防戦略の確立につながると考えられる。また、性ホルモンの制御を担うSHBGに新たな生理活性があることを示したことは、性と代謝との関連を理解するための重要な知見と考えられる。

Report

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

    (5 results)

All 2020 2019 2018 2017

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

  • [Journal Article] Correlation among body composition and metabolic regulation in a male mouse model of Cushing’s syndrome2020

    • Author(s)
      Uehara M, Yamazaki H, Yoshikawa N, Kuribara-Souta A, Tanaka H
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 1 Pages: 21-30

    • DOI

      10.1507/endocrj.EJ19-0205

    • NAID

      130007790982

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages2018

    • Author(s)
      Yamazaki Hiroki、Kushiyama Akifumi、Sakoda Hideyuki、Fujishiro Midori、Yamamotoya Takeshi、Nakatsu Yusuke、Kikuchi Takako、Kaneko Sunao、Tanaka Hirotoshi、Asano Tomoichiro
    • Journal Title

      Mediators of Inflammation

      Volume: 2018 Pages: 1-12

    • DOI

      10.1155/2018/3062319

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 肥満に伴う代謝異常と骨格筋トランスクリプトームとの関連の解析2019

    • Author(s)
      山崎広貴、栗原明子、吉川賢忠、上原昌晃、西村茉優、山本元久、田中廣壽
    • Organizer
      日本筋学会第5回学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 骨格筋におけるステロイド作用の解明から 生体システムの統合的理解へ2019

    • Author(s)
      山崎広貴、吉川賢忠、田中廣壽
    • Organizer
      第74回日本体力医学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Inhibitory effect of sex hormone-binding globulin on lipid storage of adipocytes and on inflammation of both adipocytes and macrophages2017

    • Author(s)
      Hiroki Yamazaki, Akifumi Kushiyama, Tomoichiro Asano, Toshiki Eri, Noriaki Shimizu, Noritada Yoshikawa, Hirotoshi Tanaka.
    • Organizer
      12th International Symposium of the Institute Network
    • Related Report
      2017 Research-status Report

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

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