| Project/Area Number |
25461360
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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 |
Metabolomics
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Takeshi 熊本大学, 医学部附属病院, 講師 (20398192)
NISHIKAWA Takeshi 独立行政法人国立病院機構熊本医療センター(臨床研究部), その他部局等, その他 (70336212)
KONDO Tatsuya 熊本大学, 生命科学研究部, 講師 (70398204)
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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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肥満 / 脂肪細胞 / TNF-R1 / 炎症 / サイトカイン / メタボリックシンドローム / インスリン抵抗性 / ２型糖尿病 / TNF１型受容体 / ADAM-8 / ２型糖尿病発症 |
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| Outline of Final Research Achievements |
TNFα is involved in obesity-induced insulin resistance. The biological activities are mediated via two distinct receptors, TNFR1 and TNFR2. TNFR1 mainly initiates either pro-inflammatory or pro-apoptotic signals in many tissues. A previous work demonstrated that a disintegrin and metalloproteinase 8 (ADAM8) works as a TNFR1 sheddase and produced neuro-protections. However, it has not been tested whether ADAM8 cleaves TNFR1 in adipose and liver tissues in obesity. We investigated whether AMAM8 affects TNFR1 shedding to measure TNFR1 in cell experiments. Both of diet-induced obesity and gold-thioglucose-induced hyperphagic mice showed increased expression of ADAM8 mRNA. Either TNFα or LPS treatment increased TNFR1 shedding in 3T3-L1 and HepG2 cells. However, adenoviral overexpression of ADAM8 or addition of purified ADAM8 protein to culture media did not affect TNFα- or LPS-induced TNFR1 shedding, indicated that ADAM8 may not work as a TNFR1 sheddase in adipocytes and liver.
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