Cbl-b Is a Critical Regulator of Macrophage Activation Associated With Obesity-Induced Insulin Resistance in Mice

• Material Type: 博士論文
• Title: Cbl-b Is a Critical Regulator of Macrophage Activation Associated With Obesity-Induced Insulin Resistance in Mice
• Author/Editor: Abe, Tomoki; Hirasaka, Katsuya; Kagawa, Sachiko; Kohno, Shohei; Ochi, Arisa; Utsunomiya, Kenro; Sakai, Atsuko; Ohno, Ayako; Teshima-Kondo, Shigetada; Okumura, Yuushi; Oarada, Motoko; Maekawa, Yoichi; Terao, Junji; Mills, Edward M.; Nikawa, Takeshi
• Author Heading: Abe, Tomoki; Hirasaka, Katsuya; Kagawa, Sachiko; Kohno, Shohei; Ochi, Arisa; Utsunomiya, Kenro; Sakai, Atsuko; Ohno, Ayako; Teshima-Kondo, Shigetada; Okumura, Yuushi; Oarada, Motoko; Maekawa, Yoichi; Terao, Junji; Mills, Edward M.; Nikawa, Takeshi
• Publication, Distribution, etc.: American Diabetes Association
• Publication Date: 2013-06-01
• Publication Date (W3CDTF): 2013-06-01
• Alternative Title: 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
• Periodical title: Diabetes
• No. or year of volume/issue: 62 6
• Volume: 62
• Issue: 6
• Pages: 1957-1969
• ISSN (Periodical Title): ISSN : 0012-1797; ISSN : 1939-327X
• Degree grantor/type: 徳島大学
• Date Granted: 2014-03-24
• Dissertation Number: 甲第2676号
• Degree Type: 博士（栄養学）
• Text Language Code: eng
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Source: fulltext; http://repo.lib.tokushima-u.ac.jp/files/public/10/106157/20170929145338210285/LID201405161003.pdf; http://repo.lib.tokushima-u.ac.jp/files/public/10/106157/20200313114952405635/k2676_fulltext.pdf
• Access Restrictions: インターネット公開
• Rights (production): © 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.
• Related Material (DOI): 10.2337/db12-0677
• Periodical Title (NCID): AA00628057; https://ci.nii.ac.jp/ncid/AA00628057; AA12037590; https://ci.nii.ac.jp/ncid/AA12037590
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ