| Project/Area Number |
18K06525
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 46030:Function of nervous system-related
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| Research Institution | Keio University |
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Principal Investigator |
SUYAMA Shigetomo 慶應義塾大学, 医学部(信濃町), 特任助教 (80528414)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 摂食・エネルギー代謝 / 視床下部 / シナプス / C１qファミリータンパク質 / エネルギー代謝 / シナプス形成分子 / シナプス可塑性 / 摂食 / 補体C１qファミリー / C1qファミリー |
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| Outline of Final Research Achievements |
C1q family proteins are secreted from presynaptic terminals, accumulate neurotransmitter receptors, and play a role in synaptogenesis and transmission regulation. The hypothalamic huger / satiety center receives and integrates peripheral energy metabolism information (hormones, nutrients) to maintain energy metabolism homeostasis. Focusing on C1ql3 and Cbln4, which belong to the C1q family, we investigated their contribution to systemic energy metabolism through synaptic transmission of hypothalamic neurons.
C1ql3 is expressed in the lateral hypothalamus, arcuate nucleus, paraventricular nucleus and pancreatic islet, and C1ql3 deficient mice show significant overeating after fasting and marked glucose tolerance. Cbln4 was observed on the axons of AgRP neurons, which are orexigenic neurons in the arcuate nucleus of the hypothalamus, accumulates at synapses by fasting, and regulates inhibitory synaptic transmission.
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| Academic Significance and Societal Importance of the Research Achievements |
視床下部の満腹・摂食中枢は食欲・エネルギー消費のバランスをとり、全身のエネルギー恒常性の維持を担う。その神経回路網はシナプス可塑性により、全身エネルギー状態（空腹/満腹など）を反映して、動的に再編される。その可塑性の分子機序の解明を目指し、全身エネルギー状態の変化によるシナプス形成分子C1ql3,Cbln4の局在変化とその欠損による表現型の変化を見出した。過食・肥満などのメタボリックな病態ではこの可塑性に異常が起こることが知られており、本研究成果は新規の治療標的につながることが期待される。
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