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Research on mechanism of systemic energy metabolism by glucocorticoids

Research Project

Project/Area Number 16H05330
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionThe University of Tokyo

Principal Investigator

Tanaka Hirotoshi  東京大学, 医科学研究所, 教授 (00171794)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords代謝学 / 内分泌学 / エネルギー代謝 / 骨格筋 / 臓器連関 / グルココルチコイド / 多臓器連関 / 副腎皮質 / 遺伝子発現 / 視床下部下垂体副腎系 / 核内レセプター / 内科 / 遺伝子 / 生物・生体工学 / 生理学 / シグナル伝達 / 糖尿病 / 生活習慣病 / 肥満 / クッシング症候群
Outline of Final Research Achievements

We investigated the physiological significance of glucocorticoid (GC) in skeletal muscle metabolism and function, focusing on GC receptor (GR)-mediated gene expression. The role of the signal axis between skeletal muscle, liver, and adipose tissue in the control of whole body energy metabolism was clarified by the inhibitory effects on muscle protein degradation and liver and adipose tissue metabolism. Using Cushing's syndrome model mice and ob/ob mice, we found that molecules other than alanine and FGF21 were also involved as key factors in the skeletal muscle-liver-fat axis. From the above, it was shown that the energy metabolism at the individual level is precisely controlled by various factors via inter-organ interaction according to the metabolic state.

Academic Significance and Societal Importance of the Research Achievements

申請者が開発した骨格筋特異的GR遺伝子破壊マウスは内分泌シグナルによって制御される骨格筋タンパク分解代謝を欠損したモデルであり、内分泌-代謝と運動の連関、複数臓器の機能的連関を介した生体制御、を解析可能とする画期的ツールである。本研究により、GCによる骨格筋を起点とした多系統・多臓器連携の解明を通じて個体レベルのエネルギーフロー調節機構が理解され、生体恒常性維持の基盤に関わる内分泌学理構築につながる。また、肥満、糖尿病などの「エネルギーフロー異常を伴う病気」において、従来のパラダイムを超えた新規分子マーカー発見、新規食事・薬物療法の開発など画期的新展開をもたらす可能性がある。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (39 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 12 results,  Acknowledgement Compliant: 5 results) Presentation (20 results) (of which Int'l Joint Research: 3 results,  Invited: 18 results) Remarks (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] Differences in clinical features of IgG4-related disease between elderly and younger patients2019

    • Author(s)
      Yamamoto M, Takahashi H, Tanaka H
    • Journal Title

      Geriatr Gerontol Int

      Volume: 19 Issue: 6 Pages: 564-565

    • DOI

      10.1111/ggi.13662

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pressure overload inhibits glucocorticoid receptor transcriptional activity in cardiomyocytes and promotes pathological cardiac hypertrophy2019

    • Author(s)
      Matsuhashi Tomohiro、Endo Jin、Katsumata Yoshinori、Yamamoto Tsunehisa、Shimizu Noriaki、Yoshikawa Noritada、Kataoka Masaharu、Isobe Sarasa、Moriyama Hidenori、Goto Shinichi、Fukuda Keiichi、Tanaka Hirotoshi、Sano Motoaki
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 130 Pages: 122-130

    • DOI

      10.1016/j.yjmcc.2019.03.019

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GLCCI1 is a novel protector against glucocorticoid-induced apoptosis in T cells2019

    • Author(s)
      Zentaro Kiuchi, Yukino Nishibori, Satoru Kutsuna, et al.
    • Journal Title

      FASEB J

      Volume: 33 Issue: 6 Pages: 7387-7402

    • DOI

      10.1096/fj.201800344rr

    • Related Report
      2019 Annual Research Report 2018 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation2018

    • Author(s)
      K. Anan, S. Hino, N. Shimizu, A. Sakamoto, K. Nagaoka, R. Takase, K. Kohrogi, H. Araki, Y. Hino, S. Usuki, S. Oki, H. Tanaka, K. Nakamura, F. Endo, and M. Nakao
    • Journal Title

      Nucleic Acids Res.

      Volume: 18 Issue: 11 Pages: 5441-5454

    • DOI

      10.1093/nar/gky234

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice2018

    • Author(s)
      Usui Yuki、Kimura Yasumasa、Satoh Takeshi、Takemura Naoki、Ouchi Yasuo、Ohmiya Hiroko、Kobayashi Kyosuke、Suzuki Hiromi、Koyama Satomi、Hagiwara Satoko、Tanaka Hirotoshi、Imoto Seiya、Eberl G?rard、Asami Yukio、Fujimoto Kosuke、Uematsu Satoshi
    • Journal Title

      International Immunology

      Volume: 30 Issue: 7 Pages: 319-331

    • DOI

      10.1093/intimm/dxy035

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation2018

    • Author(s)
      Kotaro Anan, Shinjiro Hino, Noriaki Shimizu, Akihisa Sakamoto, Katsuya Nagaoka, Ryuta Takase, Kensaku Kohrogi, Hirotaka Araki, Yuko Hino, Shingo Usuki, Shinya Oki, Hirotoshi Tanaka, Kimitoshi Nakamura, Fumio Endo, Mitsuyoshi Nakao
    • Journal Title

      Nucleic Acid Res

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of skeletal muscle glucocorticoid receptor in systemic energy homeostasis2017

    • Author(s)
      Tanaka Hirotoshi、Shimizu Noriaki、Yoshikawa Noritada
    • Journal Title

      Experimental Cell Research

      Volume: 360 Issue: 1 Pages: 24-26

    • DOI

      10.1016/j.yexcr.2017.03.049

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells.2017

    • Author(s)
      Naoki Ito, Isao Kii, Noriaki Shimizu, Hirotoshi Tanaka and Shin’ichi Takeda
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 8097-8097

    • DOI

      10.1038/s41598-017-08232-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure2017

    • Author(s)
      Ono T, Kamimura N, Matsuhashi T, Nagai T, Nishiyama T, Endo J, Hishiki T, Nakanishi T, Shimizu N, Tanaka H, Ohta S, Suematsu M, Ieda M, Sano M, Fukuda K, Kaneda R
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 39752-39752

    • DOI

      10.1038/srep39752

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A rheumatoid arthritis patient complicated with adenine phosphoribosyltransferase deficiency and unilateral renal agenesis: a first case report2017

    • Author(s)
      Matsubara Erika、Yoshikawa Noritada、Hosono Osamu、Baba Hiroyuki、Eri Toshiki、Uehara Masaaki、Oda Aya、Sekita Chieko、Taniguchi Atsuo、Tanaka Hirotoshi
    • Journal Title

      Modern Rheumatology Case Reports

      Volume: 1 Issue: 1 Pages: 15-19

    • DOI

      10.1080/24725625.2016.1266729

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1+CXCR5-/dim B-helper T cell induction2017

    • Author(s)
      Toshiki Eri, Kimito Kawahata, Takeyuki Kanzaki, Mitsuru Imamura, Kazuya Michishita, Lisa Akahira, Ei Bannai, Noritada Yoshikawa, Yasumasa Kimura, Takeshi Satoh, Satoshi Uematsu, Hirotoshi Tanaka, and Kazuhiko Yamamoto
    • Journal Title

      Sci Rep

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The effects of bolus supplementation of branched-chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment2017

    • Author(s)
      Yoshikawa N, Shimizu N, Uehara M, Oda Y, Matsumiya R, Matsubara E, Kobayashi H, Hosono O, Kuribara-Souta A, Baba H, Nagamura F, Kiryu S, Tanaka H
    • Journal Title

      Modern Rheumatology

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The effects of bolus supplementation of branched-chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment2016

    • Author(s)
      Yoshikawa N, Shimizu N (equal first author), Uehara M, Oda A, Matsumiya R, Matsubara E, Kobayashi H, Hosono O, Kuribara-Souta A, Baba H, Nagamura F, Kiryu S, Tanaka H
    • Journal Title

      Modern Rheumatology

      Volume: Epub ahead of print Issue: 3 Pages: 508-517

    • DOI

      10.1080/14397595.2016.1213480

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enhancement of Satellite Cell Transplantation Efficiency by Leukemia Inhibitory Factor2016

    • Author(s)
      Ito N, Shimizu N, Tanaka H, Takeda S
    • Journal Title

      J Neuromuscul Dis

      Volume: 3 Pages: 201-207

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 特別講演「ステロイドのエッセンス」2019

    • Author(s)
      田中 廣壽
    • Organizer
      第30回日本リウマチ学会中国・四国支部学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨格筋サイエンスの新展開2019

    • Author(s)
      田中 廣壽
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Glucocorticoid receptor today2019

    • Author(s)
      田中 廣壽
    • Organizer
      The Fifth Symposium of the Korean Adrenal Gland and Endocrine Hypertension Study Group
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel aspects of glucocorticoid receptor in physiology2019

    • Author(s)
      田中 廣壽
    • Organizer
      Steroid Today 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] リウマチ膠原病臨床と骨格筋のサイエンス2019

    • Author(s)
      田中 廣壽
    • Organizer
      RA治療セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ステロイドによる筋萎縮の分子機構解明と臨床への橋渡し、そして骨格筋の新しい役割の解明へ2018

    • Author(s)
      田中 廣壽
    • Organizer
      愛媛大学プロテオサイエンスセンター学術シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨格筋と肥満2018

    • Author(s)
      田中廣壽
    • Organizer
      第16回肥満症カンファレンス
    • Related Report
      2018 Annual Research Report
  • [Presentation] 免疫代謝内分泌に関わる臓器連関2018

    • Author(s)
      田中 廣壽
    • Organizer
      免疫・代謝・内分泌アカデミアフォーラム2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Skeletal muscle glucocorticoid receptor and systemic energy metabolism2018

    • Author(s)
      田中 廣壽
    • Organizer
      4th Congress on Steroid Research 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ステロイドによる筋萎縮の分子機構解明と臨床への橋渡し、そして骨格筋の新しい役割の解明へ2018

    • Author(s)
      田中 廣壽
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ステロイドの使い方2017

    • Author(s)
      田中廣壽
    • Organizer
      第27回日本医療薬学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アミノ酸研究の新展開 - 多臓器相関を介したエネルギー 代謝における役割2017

    • Author(s)
      田中廣壽
    • Organizer
      日本アミノ酸学会 第11回 学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Plenary Lecture「Skeletal muscle glucocorticoid receptor and systemic energy metabolism」2017

    • Author(s)
      田中廣壽
    • Organizer
      10th International Meeting of Pediatric Endocrinology
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] メカノーメタボカップリングー 骨格筋研究から多臓器連関による生体エネルギー制御機構の理解へ2017

    • Author(s)
      田中廣壽
    • Organizer
      第35回日本骨代謝学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 特別講演「ステロイドのサイエンスと臨床」2017

    • Author(s)
      田中廣壽
    • Organizer
      第52回 日本小児腎臓病学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨格筋GRとメカノーメタホカッフリンク2016

    • Author(s)
      田中廣壽
    • Organizer
      第24回 日本ステロイドホルモン学会学術集会
    • Place of Presentation
      大分市、日本
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 臓器間連携を介したエネルギー代謝制御における骨格筋グルココルチコイド受容体の役割2016

    • Author(s)
      清水宣明
    • Organizer
      第24回 日本ステロイドホルモン学会学術集会
    • Place of Presentation
      大分市、日本
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨格筋グルココルチコイド受容体を介した個体レベルの脂質代謝制御2016

    • Author(s)
      清水宣明,田中廣壽他
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      横浜市、日本
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨格筋-肝臓-脂肪組織シグナル軸とメカノ-メタボカップリング2016

    • Author(s)
      清水宣明,田中廣壽他
    • Organizer
      第2回 日本筋学会学術集会
    • Place of Presentation
      小平市、日本
    • Year and Date
      2016-08-05
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mechano-Metabo Coupling: Skeletal muscle volume regulation and systemic energy metabolism2016

    • Author(s)
      田中廣壽
    • Organizer
      第59回 日本糖尿病学会年次学術集会
    • Place of Presentation
      京都市、日本
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks] 研究紹介

    • URL

      https://www.ims.u-tokyo.ac.jp/Rheumatol/allergy/research.html

    • Related Report
      2019 Annual Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/Rheumatol/allergy/research.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京大学医科学研究所附属病院アレルギー免疫科、抗体・ワクチンセンター免疫病治療学分野 研究紹介

    • URL

      http://www.ims.u-tokyo.ac.jp/Rheumatol/allergy/research.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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