| Project/Area Number |
16K19532
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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
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| Research Institution | University of Toyama |
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Principal Investigator |
Watanabe Yasuharu 富山大学, 大学院医学薬学研究部(医学), 客員准教授 (80646307)
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| Research Collaborator |
NAGAI Yoshinori 富山県立大学, 工学部, 教授 (30431761)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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 | 好中球 / 脂肪細胞 / IL-1 beta / 内臓脂肪組織 / 炎症 / 脂肪組織 / 脂肪酸 |
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| Outline of Final Research Achievements |
Obesity-associated adipose tissue inflammation contributes to the development of type 2 diabetes. In obese adipose tissue, free fatty acids (FFAs) are released from hypertrophied adipocytes and considered as trigger for adipose tissue inflammation by recruiting immune cells including macrophages. In this study, we found that FFAs induce the infiltration of neutrophils into adipose tissue via LTB4 production from adipose tissue. Infiltrated neutrophils interacted with adipocytes and increased pro-IL-1 beta expression through NF-kappa B pathway activation. IL-1 beta was produced from neutrophils and induced S100A8 production from adipocytes, which promoted macrophage infiltration into adipose tissue and exacerbated the inflammation. We have provided novel insights related to adipose tissue neutrophils and IL-1 beta, and dissected their roles in the initiation of adipose tissue inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
研究代表者は、遊離脂肪酸の増加が1つのトリガーとなり、好中球がVATに浸潤し、脂肪細胞と相互作用することによりVAT炎症やマクロファージの浸潤に関与する一連のVAT炎症の誘導機序を見出した。本研究により、好中球はマクロファージよりも早期のVAT炎症に大きく寄与していることから、好中球は2型糖尿病の予防薬や機能性食品のターゲットの１つになりうることが示唆された。
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