The decreased thermogenic activity in brown fat during the development of obesity
| Project/Area Number |
20K19709
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KURODA Masashi 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (00803579)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 褐色脂肪細胞 / エネルギー代謝 / 熱産生 / 肥満 / メタボリックシンドローム |
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| Outline of Research at the Start |
まず褐色脂肪細胞IRF7が高脂肪食によって実際に活性化するかを確認し、単離褐色脂肪細胞での過剰発現系にてIRF7の意義を評価する。遺伝子改変動物を用いて個体エネルギー代謝に対する褐色脂肪IRF7の寄与を検討し、IRF7活性化に関与する因子の同定や褐色脂肪機能抑制の分子機序の解明に取り組む。得た知見をもとにマウスへ薬剤投与を行い、肥満治療・予防応用への可能性を探る。
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| Outline of Final Research Achievements |
Energy expenditure for thermogenesis in brown adipose tissue serves to maintain whole body energy homeostasis, but during the development of obesity, this thermogenic function is impaired. In this study, by combining DNA microarray analysis of brown fat, and the prediction of transcription factor binding analysis, we have identified the transcription factor, IRF7 (Interferon Reguratory Factor 7) as a possible suppressor for thermogenesis in brown fat.
IRF7 knockout mice showed increased expression of thermogenic genes in brown adipose and were more resistant to a cold enviroment than wild type control. Also, under high fat feeding condition, knockout mice showed improved adiposity and glucose tolerance. These data indicate that IRF7 is associated with the decreased thermogenic activity during the development of obesity.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満形成における褐色脂肪機能不全については、褐色脂肪組織内での炎症や過剰な酸化・小胞体ストレスの関与が指摘されてきた。炎症や種々のストレスは肥満ともに進展し、熱産生低下の増悪因子であると考えらえるが、実際には炎症・ストレスマーカー遺伝子が誘導されない程度の短期間マウスへ高脂肪食を給餌した際にも、既に熱産生関連遺伝子の抑制が生じていることから根本的な原因とは考えにくい。本研究は肥満に関わる褐色脂肪機能不全について、より本質的なメカニズムを明らかにし、肥満予防・治療法の確立に向けた基礎知見の獲得を試みた。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model.2021
Author(s)
Morio A, Tsutsumi R, Satomi S, Kondo T, Miyoshi H, Kato T, Kuroda M, Kitamura T, Hara K, Saeki N, Sakaue H, and Tsutsumi YM
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Journal Title
Diabetol Metab Syndr
Volume: 13
Issue: 1
Pages: 39-39
DOI
Related Report
Peer Reviewed
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[Journal Article] Leucine induces cardioprotection in vitro by promoting mitochondrial function via mTOR and Opa-1 signaling.2021
Author(s)
Morio A, Tsutsumi R, Kondo T, Miyoshi H, Kato T, Narasaki S, Satomi S, Nakaya E, Kuroda M, Sakaue H, Kitamura T, Tsutsumi YM
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Journal Title
Nutr Metab Cardiovasc Dis
Volume: 31
Issue: 10
Pages: 2979-2986
DOI
Related Report
Peer Reviewed
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[Journal Article] The PDK1-FoxO1 Signaling in Adipocytes Controls Systemic Insulin Sensitivity Through the 5-lipoxygenase-leukotriene B 4 Axis2020
Author(s)
Hosooka T, Hosokawa Y, Matsugi K, Shinohara M, Senga Y, Tamori Y, Aoki C, Matsui S, Sasaki T, Kitamura T, Kuroda M, Sakaue H, Nomura K, Yoshino K, Nabatame Y, Itoh Y, Yamaguchi K, Hayashi Y, Nakae J, Accili D, Yokomizo T, Seino S, Kasuga M, Ogawa W.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: Online ahead of print
Issue: 21
Pages: 11674-11684
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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