| Project/Area Number |
24500494
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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 |
Laboratory animal science
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| Research Institution | Rakuno Gakuen University (2014)
Nagoya City University (2012-2013) |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
MIYOSHI Ichiro 東北大学, 大学院医学系研究科, 教授 (10183972)
OKAMOTO Shiki 自然科学研究機構, 生理学研究所, 助教 (40342919)
NAOE Yoshinori 国立長寿医療研究センター研究所, 研究員 (50392048)
TAKAHASI Eiki 理化学研究所, 脳科学総合研究センター, ユニットリーダー (40446521)
IWANAGA Toshihiko 北海道大学, 大学院医学研究科, 教授 (10160128)
KIMURA Shunsuke 北海道大学, 大学院医学研究科, 助教 (40444525)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | マクロファージ / 糖尿病 / 炎症 / トランスジェニックマウス / ノックアウトマウス / 脂肪組織 / 遺伝子発現 / 糖代謝 / 遺伝子組換えマウス / 核内タンパク質 / 慢性炎症 / ２型糖尿病 / 遺伝子組み換えマウス / 肥満 / ob/obマウス |
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| Outline of Final Research Achievements |
1) In ob/ob mice, M-mod/USP2A expression was clearly decreased in adipose tissue macrophages whereas aP2 and PAI were increased. Transgenic mice selectively expressing M-mod in macrophages did not exhibited significant changes in body weight gain, blood glucose levels, and blood insulin levels after high fat diet for 3 months. On the other hand, the M-mod transgenic mice displayed decreased accumulation of macrophages in visceral adipose tissues in parallel with decreased expression of chemokines in macrophages. In addition, M-mod overexpression in macrophages for 1 year caused decreased body weight gain and improved insulin sensitivity. Thus, M-mod seems to be a potent attenuator of type 2 diabetes.
2) M-mod knockdown macrophage-like cells modulated acetylation and methylation of histone near the M-mod-targeting genes such as aP2. Moreover, we found several nuclear proteins directly associated with M-mod in macrophages.
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