| Project/Area Number |
16K21318
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
Experimental pathology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肥満 / リポ蛋白リパーゼ / マクロファージ / 炎症 / 線維化 / 脂質 / 酵素 / 細胞・組織 / 遺伝子 / 糖尿病 |
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| Outline of Final Research Achievements |
Macrophages control inflammation and fibrosis in adipose tissues. To understand the role of LpL secreted from adipose tissue macrophages (ATMs) in obesity, we generated leptin-deficient ob/ob mice lacking LpL in myeloid cells (MLpLKO:ob/ob). MLpLKO:ob/ob gained less body weight primarily due to a decrease in subcutaneous fat, ate less food and were more insulin-sensitive, but were more hypertriglyceridemic due to lower LPL activity in post-heparin plasma than ob/ob mice. Notably, MLpLKO:ob/ob showed enlarged crown-like structures and substantial worsening of fibrosis in white adipose tissues. The ATMs from MLpLKO:ob/ob showed increased expression of the genes related to fibrosis (e.g. TGFβ1 and TIMP1), inflammation and efferocytosis. In conclusion, the loss of myeloid LpL converts the ATMs to a more fibrogenic phenotype, thereby contributing to the extensive fibrosis in adipose tissues and resistance to obesity in ob/ob background.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満形成に伴う慢性炎症において、脂肪組織に集積するマクロファージが重要な役割を果たす。マクロファージLpLを欠損したマウスでは肥満を誘導すると白色脂肪組織に顕著な細胞浸潤と線維化を呈した。その機序として、肥満では脂肪組織マクロファージのLpLが欠損するとことにより、マクロファージが線維化誘導性に形質転換することによると考えられた。したがって脂肪組織マクロファージLpLは脂肪組織の線維化を抑制することが明らかになった。これらの結果は、脂肪組織線維化のメカニズムの理解を深めるのに有意義なものと考えられる。
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