Hepatic insulin action affects energy expenditure
| Project/Area Number |
19K17951
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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 54040:Metabolism and endocrinology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Takahashi Kei 東北大学, 医学系研究科, 助教 (00644808)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肝臓 / インスリン作用 / エネルギー摂取 / エネルギー消費 / 熱産生 / インスリン作用低下 / 褐色脂肪組織熱産生 / 糖尿病 / 内科 / 臨床 |
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| Outline of Research at the Start |
まず、iLIRKOマウスのエネルギー消費が低下する機序の解明と脳におけるレプチン作用低下の詳細な検討を行う。続いて、iLIRKOマウスにおける肝臓―脳の連関を担う分子機構の解明を行う。さらに、肥満状態や飢餓状態の際、本メカニズムがどのように機能し、餌を与えた際の摂食行動に影響するかを検討する。
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| Outline of Final Research Achievements |
We attempted to elucidate what happens when insulin action in the liver becomes decreased. Particularly, we studied the effects of decreased hepatic insulin action on systemic energy metabolism. We discovered that decreased insulin action in the liver reduces leptin action in the hypothalamus, increases food intake, decreases sympathetic-driven BAT thermogenesis, which altogether results in body weight gain.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病は肥満の合併が多いが、根治療法が存在せず、特に食行動変容を伴う場合は、コントロールが非常に困難である。本研究で発見した新規の肝臓－脳－褐色脂肪組織連関は、糖尿病や肥満の病態の理解を深め、食欲や食行動異常の制御を可能とする新たな治療法の創出に発展する可能性があり、創薬の観点でも創造的である。
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Inhibition of Plasminogen Activator Inhibitor-1 Activation Suppresses High Fat Diet-Induced Weight Gain via Alleviation of Hypothalamic Leptin Resistance2020
Author(s)
Shinichiro Hosaka, Tetsuya Yamada, Kei Takahashi, Takashi Dan, Keizo Kaneko, Shinjiro Kodama, Yoichiro Asai, Yuichiro Munakata, Akira Endo, Hiroto Sugawara, Yohei Kawana, Junpei Yamamoto, Tomohito Izumi, Shojiro Sawada, Junta Imai, Toshio Miyata and Hideki Katagiri
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Journal Title
Front Pharmacol.
Volume: 11
Pages: 943-943
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16.2019
Author(s)
Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue MK, Mizuno Y, Nakanishi M, Sano T, Yamawaki Y, Kushiyama A, Sakoda H, Fujishiro M, Ryo A, Ono H, Minamino T, Takahashi SI, Ohno H, Yoneda M, Takahashi K, Ishihara H, Katagiri H, Nishimura F, Kanematsu T, Yamada T, Asano T.
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Journal Title
Cell Rep.
Volume: 26
Issue: 12
Pages: 3221-3230
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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