Impacts of pericyte behavior on vascular niche maintaining adipocyte progenitor cells in obesity
| Project/Area Number |
17H06705
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Toyama |
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Principal Investigator |
Onogi Yasuhiro 富山大学, 大学院医学薬学研究部(薬学), 研究員 (80801761)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 脂肪組織肥大化機構 / 血管新生 / 脂肪幹細胞 / マクロファージ / ペリサイト / PDGF / 肥満進展機構 / 血管リモデリング / 肥満 / 脂肪組織 / 血小板由来増殖因子 / 糖代謝 / 細胞・組織 / 糖尿病 |
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| Outline of Final Research Achievements |
We studied how obesity-related three events, namely accumulation of pro-inflammatory macrophages, angiogenesis and adipogenesis from adipocyte progenitor cells, coordinately involve in the expansion of white adipose tissue (WAT) expansion. Pro-inflammatory-activated ERK signaling pathway coupled with glycolysis induced Pdgfb mRNA expression in macrophages. Diet-induced WAT expansion was prevented in mice depleted adipose tissue macrophages with prevention of pericytes dissociation from vessels and neovascularization. The number of adipocyte progenitor cells in WAT was decreased in this condition compared to that in control mice. These findings suggest that pro-inflammatory macrophages accumulated close to vasculature remodel vascular networks by exposing abundant PDGF-B against pericytes within obese WAT. In addition, adipocyte progenitor cells appear to proliferate within the microenvironment where vascular remodeling occurs during obesity.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満関連疾患の克服は、本邦のみならず全世界で解決すべき課題である。肥満病態の進展機構の理解は、肥満に起因する疾患の治療戦略構築の基礎となりえる。肥大化した脂肪組織に集積する炎症性マクロファージによる慢性炎症は、肥満関連疾患の引き金となることが明らかになってきている。それに加えて、本知見は炎症性マクロファージが血管を再構築することで、新たな脂肪細胞を生成する環境を生み出すことを見出した。また、炎症性マクロファージは高血糖下においてより活性化する知見を踏まえると、本研究は、肥満・高血糖病態での血糖降下療法の重要性を示すことに加え、マクロファージの活性制御を標的とした新規治療戦略の可能性を提示する。
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Report
(3 results)
Research Products
(8 results)
