| Project/Area Number |
22KF0422
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| Project/Area Number (Other) |
21F21406 (2021-2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2021-2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | National Institutes of Natural Sciences |
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Principal Investigator |
根本 知己 大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 教授 (50291084)
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| Co-Investigator(Kenkyū-buntansha) |
LEE MING-LIANG 大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2023: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2022: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2021: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | Body temperature / glucose metabolism / QIH / torpor / hypothermia / glucose sensing / body temperature / Q-neuron / hypometabolism |
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| Outline of Research at the Start |
We first study the glucose homeostasis of Q-neuron-induced hypothermia and hypometabolism (QIH) mice such as glucose expenditure and gluconeogenesis in QIH animals. Because QIH decreases heat production and body temperature, relationship between body temperature of glucose metabolism was also studied. We also investigate brain glucose sensing in QIH animals by using in vivo calcium imaging. Finally, glucose-sensing neurons in QIH mice will be artificially activated to understand the role of these neurons in regulation of glucose metabolism.
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| Outline of Annual Research Achievements |
Using the QIH model, we found that QIH mice are glucose hypometabolic with insulin resistance. These QIH mice were pyruvate intolerant, but lower liver PEPCK expression suggested lower gluconeogenesis after fasting. The 2DG uptake assay indicated extremely reduced glucose utilization and insulin sensitivity in peripheral tissues. The net effect of lower glucose production and utilization resulted in higher fasting blood glucose and pyruvate intolerance in QIH mice. Increasing the body temperature of QIH mice by raising the ambient temperature improved glucose metabolism, whereas raising the ambient temperature did not significantly affect glucose metabolism in the control animal. Taken together, body temperature rather than ambient temperature is a strong factor to regulate glucose metabolism. In addition, food intake and locomotor activity, which are severely affected by QIH-mediated hypothermia, were also restored by increasing body temperature. We conclude that the QIH-mediated glucose hypometabolism and torpid behavior are regulated by hypothermia rather than Qrfp neurons, and body temperature rather than ambient temperature is a strong factor to regulate physiological responses. A manuscript regarding the above results has been submitted to peer-reviewed academic journals.
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