| Project/Area Number |
25460369
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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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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
FUKUDA Daiju 徳島大学, 大学院医歯薬学研究部, 特任講師 (40637568)
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| Co-Investigator(Kenkyū-buntansha) |
SATA Masataka 徳島大学, 大学院医歯薬学研究部, 教授 (80345214)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 炎症 / マクロファージ / インスリン抵抗性 / ＴＬＲ９ / 肥満 / 脂肪 |
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| Outline of Final Research Achievements |
Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains obscure. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed higher plasma cfDNA levels. cfDNA released from degenerated adipocytes promoted MCP-1expression in wild-type macrophages, but not in TLR9-deficient macrophages. In fat-fed wild-type mice, genetic deletion of Tlr9 or administration of a specific TLR9 antagonist demonstrated reduced adipose tissue inflammation and better insulin sensitivity compared with the control mice. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.
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