Analysis of a novel metabolic syndrome model mouse and its molecular mechanism

新型代谢综合征模型小鼠及其分子机制分析

• 批准号: 21500386
• 负责人: ISHII Tetsuro
• 金额: $ 2.91万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21500386/
• 关键词: 疾患モデル; sequestosome1; レプチン; 肥満; 視床下部; 過食; Seuestosome 1; A170; エストラジオール; 摂食; 紫外線; アポトーシス; sequestosome 1

A mutant mouse defective in sequestosome1 gene causes mature-onset obesity. A previous study suggested importance of sequestosome1 (SQSTM1/p62) in regulation of adipocyte differentiation as a cause of obesity formation. However, our studies show overeating is the cause of the obesity formation. We constructed brain-specific SQSTM1 knock-down mouse. We found the conditional knock-down mouse exhibited similar body weight increase as the whole body gene knock-out mouse. We showed SQSTM1 is highly expressed in neurons of hypothalamus, suggesting a possibility that SQSTM1 is involved in the intracellular signaling of anorexic hormone leptin. Interesting finding is a female hormone estradiol compensates the lack of SQSTM1 in body weight control. It inhibits obesity formation through suppression of overeating of the mutant mice.

在secestosome1基因中有缺陷的突变小鼠会导致成熟发作的肥胖症。先前的一项研究表明，Secestosome1（SQSTM1/p62）在调节脂肪细胞分化作为肥胖形成的原因中的重要性。但是，我们的研究表明，暴饮暴食是肥胖形成的原因。我们构建了大脑特异性的SQSTM1敲低鼠标。我们发现有条件的敲除小鼠表现出与整个身体基因敲除小鼠相似的体重。我们显示SQSTM1在下丘脑神经元中高度表达，这表明SQSTM1可能参与厌氧激素瘦素的细胞内信号传导。有趣的发现是女性激素雌二醇可以补偿体重控制中缺乏SQSTM1。它通过抑制突变小鼠暴饮暴食而抑制肥胖的形成。

项目成果

Crucial role for autophagy in degranulation of mast cells.

• DOI: 10.1016/j.jaci.2010.12.1078
• 发表时间: 2011-05
• 期刊: The Journal of allergy and clinical immunology
• 作者: H. Ushio;T. Ueno;Y. Kojima;M. Komatsu;Satoshi Tanaka;A. Yamamoto;Yoshinobu Ichimura;J. Ezaki

Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity

• DOI: 10.1016/j.bbrc.2011.10.019
• 发表时间: 2011-11-11
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Hoshino, Tomofumi;Tabuchi, Keiji;Hara, Akira
• 通讯作者: Hara, Akira

UVB誘導性アポトーシスに対するSequestosome1/p62/A170の役割

Sequestosome1/p62/A170 对 UVB 诱导细胞凋亡的作用

• 发表时间: 2010
• 作者: 木村伸太郎;他
• 通讯作者: 他

Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis

• DOI: 10.1007/s00535-012-0552-9
• 发表时间: 2012-08-01
• 期刊: JOURNAL OF GASTROENTEROLOGY
• 影响因子: 6.3
• 作者: Okada, Kosuke;Warabi, Eiji;Shoda, Junichi
• 通讯作者: Shoda, Junichi

Enhanced neointimal hyperplasia and carotid artery remodeling in sequestosome 1 deficient mice.

Sequestosome 1 缺陷小鼠的新内膜增生和颈动脉重塑增强。

• 发表时间: 2010
• 期刊: Journal of Cellular and Molecular Medicine (印刷中)
• 作者: 朴蓮花;藤田亜美;柳涛;岳海源;蒋昌宇;水田恒太郎;友廣大輔;中塚映政;熊本栄一;Sugimoto R
• 通讯作者: Sugimoto R