アクセス数 : ?
ダウンロード数 : ?
ID 106157
タイトル別表記
Cbl-bは、マウスにおいて肥満によるインスリン抵抗性を引き起こすマクロファージ活性化の重要な調節因子である
Cbl-b DEFICIENCY AND MACROPHAGE ACTIVATION
著者
安倍, 知紀 徳島大学大学院栄養生命科学教育部(人間栄養科学専攻) KAKEN研究者をさがす
平坂, 勝也 The University of Tokushima KAKEN研究者をさがす
Kagawa, Sachiko The University of Tokushima
Kohno, Shohei The University of Tokushima
Ochi, Arisa The University of Tokushima
Utsunomiya, Kenro The University of Tokushima
Sakai, Atsuko The University of Tokushima
真板, 綾子 The University of Tokushima KAKEN研究者をさがす
奥村, 裕司 The University of Tokushima KAKEN研究者をさがす
Oarada, Motoko The University of Chiba
前川, 洋一 The University of Tokushima
Mills, Edward M. University of Texas at Austin
資料タイプ
学位論文
抄録
We previously reported the potential involvement of casitas B-cell lymphoma-b (Cbl-b) in aging-related murine insulin resistance. Because obesity also induces macrophage recruitment into adipose tissue, we elucidated here the role of Cbl-b in obesity-related insulin resistance. Cbl-b+/+ and Cbl-b-/- mice were fed a high-fat diet (HFD) and then examined for obesity-related changes in insulin signaling. The HFD caused recruitment of macrophages into adipose tissue and increased inflammatory reaction in Cbl-b-/- compared with Cbl-b+/+ mice. Peritoneal macrophages from Cbl-b-/- mice and Cbl-b–overexpressing RAW264.7 macrophages were used to examine the direct effect of saturated fatty acids (FAs) on macrophage activation. In macrophages, Cbl-b suppressed saturated FA-induced Toll-like receptor 4 (TLR4) signaling by ubiquitination and degradation of TLR4. The physiological role of Cbl-b in vivo was also examined by bone marrow transplantation and Eritoran, a TLR4 antagonist. Hematopoietic cell-specific depletion of the Cbl-b gene induced disturbed responses on insulin and glucose tolerance tests. Blockade of TLR4 signaling by Eritoran reduced fasting blood glucose and serum interleukin-6 levels in obese Cbl-b-/- mice. These results suggest that Cbl-b deficiency could exaggerate HFD-induced insulin resistance through saturated FA-mediated macrophage activation. Therefore, inhibition of TLR4 signaling is an attractive therapeutic strategy for treatment of obesity-related insulin resistance.
掲載誌名
Diabetes
ISSN
00121797
1939327X
cat書誌ID
AA00628057
AA12037590
出版者
American Diabetes Association
62
6
開始ページ
1957
終了ページ
1969
発行日
2013-06-01
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201405161003.pdf
論文本文 : k2676_fulltext.pdf
著者の申請により要約(2014-07-24公開)に替えて論文全文を公開(2020-03-13)
本論文は, 著者Tomoki Abeの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
© 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2676号
学位記番号
甲栄第210号
学位授与年月日
2014-03-24
学位名
博士(栄養学)
学位授与機関
徳島大学
部局
医学系