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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

基本信息

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

项目摘要

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.

检索酶1基因缺陷的突变小鼠会导致成熟期肥胖。先前的一项研究表明，隔离酶1(SQSTM1/p62)作为肥胖形成的原因，在调节脂肪细胞分化方面具有重要意义。然而，我们的研究表明，暴饮暴食是肥胖形成的原因。我们构建了脑特异的SQSTM1基因敲除小鼠。我们发现，条件性基因敲除小鼠的体重增加与全身基因敲除小鼠相似。我们发现SQSTM1在下丘脑的神经元中高表达，提示SQSTM1可能参与了厌食性激素瘦素的细胞内信号转导。有趣的发现是，一种女性激素雌二醇可以弥补体重控制中SQSTM1的缺乏。它通过抑制突变小鼠的过量进食来抑制肥胖的形成。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A novel mechanism of leptin resistance in sequestosome1- deficient mice.

Sequestosome1 缺陷小鼠瘦素抵抗的新机制。

DOI：
发表时间：
2009
期刊：
影响因子：
0
作者：
Harumi Harada;Eiji Warabi;Taizo Matsuki;Kosuke Okada;Toru Yanagawa;Takeshi Sakurai;Tetsuro Ishii
通讯作者：
Tetsuro Ishii

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
影响因子：
0
作者：
H. Ushio;T. Ueno;Y. Kojima;M. Komatsu;Satoshi Tanaka;A. Yamamoto;Yoshinobu Ichimura;J. Ezaki
通讯作者：
H. Ushio;T. Ueno;Y. Kojima;M. Komatsu;Satoshi Tanaka;A. Yamamoto;Yoshinobu Ichimura;J. Ezaki

COCHLEAR PROTECTION FROM ACOUSTIC INJURY BY INHIBITORS OF p38 MITOGEN-ACTIVATED PROTEIN KINASE AND SEQUESTOSOME 1 STRESS PROTEIN