Modulatory effects of macrophage M-mod/USP2 on type2 diabetes

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500494
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Rakuno Gakuen University (2014); Nagoya City University (2012-2013)
• Principal Investigator: KITAMURA Hiroshi 酪農学園大学, 獣医学群, 教授 (80312403)
• 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)
• Project Period (FY): 2012-04-01 – 2015-03-31
• 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

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.

Free Research Field

実験動物学