Proteomic analysis of rat hypothalamus revealed the role of ubiquitin-proteasome system in the genesis of DR or DIO.
Proteomic analysis of rat hypothalamus revealed the role of ubiquitin-proteasome system in the genesis of DR or DIO.
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DOI：
10.1007/s11064-011-0423-4
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发表时间：
2011-06
影响因子：
4.4
通讯作者：
Han, Ji-sheng
中科院分区：
文献类型：
--
作者：
Wang, Qi-ming;Yang, Hui;Tian, De-run;Cai, Ying;Wei, Zhong-nan;Wang, Fei;Yu, Albert Ch;Han, Ji-sheng
关键词：
肥胖已成为一种全球流行病，导致心血管疾病和2型糖尿病的负担日益增加。然而，肥胖症的确切分子机制仍不清楚。下丘脑通过整合各种营养信号在调节能量稳态中起着重要作用。本研究采用双向凝胶电泳结合基质辅助激光解吸电离飞行时间质谱（MALDI-TOF/TOF-MS）技术，对饮食诱导肥胖（DIO）和饮食抵抗（DR）大鼠下丘脑蛋白质组进行了研究。在DIO或DR大鼠的下丘脑中鉴定了22种蛋白质。这些包括代谢酶、抗氧化蛋白、蛋白酶体相关蛋白和信号蛋白，其中一些与AMP活化蛋白激酶（AMPK）信号传导或线粒体呼吸相关。在这些蛋白质中，与正常饮食组相比，泛素在DR大鼠中显著降低，但在DIO大鼠中没有变化，而泛素羧基末端酯酶L1（UCHL-1）在DIO大鼠中降低，但在DR大鼠中没有变化。使用Western印迹分析进一步验证泛素和UCHL-1的表达水平。我们的研究表明，Ubiquitin和UCHL-1是下丘脑中的肥胖相关因子，可能通过干扰控制能量平衡和进食的整合信号网络在DR或DIO的发生中发挥重要作用。
Obesity has become a global epidemic, contributing to the increasing burdens of cardiovascular disease and type 2 diabetes. However, the precise molecular mechanisms of obesity remain poorly elucidated. The hypothalamus plays a major part in regulating energy homeostasis by integrating all kinds of nutritional signals. This study investigated the hypothalamus protein profile in diet-induced obese (DIO) and diet-resistant (DR) rats using two dimensional gel electrophoresis (2-DE) combined with MALDI-TOF/TOF–MS analysis. Twenty-two proteins were identified in the hypothalamus of DIO or DR rats. These include metabolic enzymes, antioxidant proteins, proteasome related proteins, and signaling proteins, some of which are related to AMP-activated protein kinase (AMPK) signaling or mitochondrial respiration. Among these proteins, in comparison with the normal-diet group, Ubiquitin was significantly decreased in DR rats but not changed in DIO rats, while Ubiquitin carboxyl-terminal esterase L1 (UCHL-1) was decreased in DIO rats but not changed in DR rats. The expression level of Ubiquitin and UCHL-1 were further validated using Western blot analysis. Our study reveals that Ubiquitin and UCHL-1 are obesity-related factors in the hypothalamus that may play an important role in the genesis of DR or DIO by interfering with the integrated signaling network that control energy balance and feeding.
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影响因子：
5.2
作者：
Wang, Wen-Juan;Li, Qing-Quan;Xu, Jing-Da;Cao, Xi-Xi;Li, Hai-Xia;Tang, Feng;Chen, Qi;Yang, Jin-Ming;Xu, Zu-De;Liu, Xiu-Ping
通讯作者：
Liu, Xiu-Ping
影响因子：
4.8
作者：
Ko, HS;Uehara, T;Nomura, Y
通讯作者：
Nomura, Y
DOI：
10.1016/s0169-328x(03)00174-8
发表时间：
2003-07-04
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Huang, XF;Han, M;Storlien, LH
通讯作者：
Storlien, LH
DOI：
10.1016/j.bbrc.2007.02.037
发表时间：
2007-04-13
影响因子：
3.1
作者：
Berkane, Amine Adda;Nguyen, Hang Thi Thu;Hiol, Abel
通讯作者：
Hiol, Abel
糖尿病和肥胖症中的UPS。
影响因子：
--
作者：
Wing, Simon S.
通讯作者：
Wing, Simon S.