Research on mechanism of systemic energy metabolism by glucocorticoids
Project/Area Number |
16H05330
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | The University of Tokyo |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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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)
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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.
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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。
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Report
(5 results)
Research Products
(39 results)
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[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
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Journal Title
Nucleic Acids Res.
Volume: 18
Issue: 11
Pages: 5441-5454
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Nucleic Acid Res
Volume: 印刷中
Related Report
Peer Reviewed
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[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
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Journal Title
Sci Rep.
Volume: 7
Issue: 1
Pages: 39752-39752
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[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
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Journal Title
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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
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Journal Title
Modern Rheumatology
Volume: 印刷中
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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
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Journal Title
Modern Rheumatology
Volume: Epub ahead of print
Issue: 3
Pages: 508-517
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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