| Project/Area Number |
21K08549
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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 54040:Metabolism and endocrinology-related
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| Research Institution | University of Toyama |
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Principal Investigator |
Wada Tsutomu 富山大学, 学術研究部薬学・和漢系, 講師 (00419334)
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| Co-Investigator(Kenkyū-buntansha) |
笹岡 利安 富山大学, 学術研究部薬学・和漢系, 教授 (00272906)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ペリサイト / 脂肪幹細胞 / 肥満 / 脂肪組織血管 / 慢性炎症 / 分化 / 増殖 / インスリン抵抗性 |
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| Outline of Research at the Start |
肥満に伴う脂肪細胞の肥大化はインスリン感受性の低下により糖脂質代謝障害や、癌、心血管疾患、認知症などの発症や予後に関わる。これらは主に脂肪細胞の肥大化によるが、脂肪細胞数増加による肥満は代謝障害を引き起こしにくい。応募者は肥満に伴い内臓脂肪で血管新生が進むことで脂肪体積が増大することを明らかにしてきた。そこで本研究では血管新生を契機とした脂肪幹細胞の制御機構を解明し、その鍵となる幹細胞制御因子の発見に基づく新規肥満病態制御法の創出を目指す。
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| Outline of Final Research Achievements |
Increase of visceral fat is crucial in the progression of obesity; however, the underlying mechanism that controls the proliferation and differentiation of adipose stem cells remains unclear. Since adipose stem cells are maintained in the perivascular microenvironment, we hypothesized that obesity-induced detachment of pericytes may trigger the proliferation and differentiation of adipose stem cells. In the visceral adipose tissue of PDGFRb deficient mice fed a high fat diet for 8 weeks, pericytes did not detach from adipose vessels, the proliferative activity of adipose stem cells decreased, and the number of adipose stem cells decreased. In addition, pericytes suppressed adipogenic differentiation through their secreted factors. Therefore, disruption of the adipose stem cell niche by pericyte detachment appears to be important for adipose stem cell proliferation and differentiation into adipocytes in obese adipose tissue.
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| Academic Significance and Societal Importance of the Research Achievements |
内臓脂肪幹細胞ニッチの制御機構を明らかにした本研究成果は、肥満病態の理解を促進させると考えられる。さらに、代謝的に健全な肥満状態による代謝疾患予防戦略を確立するための開発基盤の強化に貢献すると期待される。
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