Diabetes：郭非凡等揭示下丘脑ATF4调控消化系统胰岛感性的新功能

昨日，国际学术期刊Diabetes在线发表了里面科院广州生科院碳水化合物科学数据分析所陈非凡组的数据分析论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该数据分析阐明了中枢神经系统活化转录生物体4 (ATF4) 通过抑制细胞核S6K色氨酸(p70 S6K1)，进而依赖功能性则有胰脏的口内真诚的分子前提，洞察了中枢神经系统ATF4恒定则有代谢稳态的插件。

2标准型冠心病是一种慢功能性代谢功能性疾病，随着生活低水平的日益提高，我国2标准型冠心病的患病率急速减低。目前关于2标准型冠心病的数据分析主要集里面在胰脏等单个骨髓，而各个骨髓的相互作用对2标准型冠心病影响的数据分析相当多。神经系统，尤其是中枢神经系统，在机体则有组织的口内真诚恒定里面起非常举足轻重的作用，近年来已逐渐带进一个数据分析同类型。ATF4是CREB后裔里面的一个举足轻重成员，之前关于ATF4介导代谢的功能数据分析主要集里面在则有组织，例如ATF4 全身敲除小鼠才会贫血，脂肪提高，单单减低，口内真诚下降时；成骨细胞里面特异功能性敲除ATF4也才会提高口内真诚等。但是神经系统里面ATF4确实参与则有口内真诚的恒定已为新闻报道。

陈非凡数据分析组的博士生张倩等人发现，通过第三脑室注射腺病毒介导的ATF4过表述只能引起胰脏的口内素压制，而显功能性突变ATF4（dominant negative-ATF4）只能提高胰脏口内真诚；有利于数据分析确认ATF4对则有糖代谢的恒定是通过中枢神经系统S6K1以及胰脏食道信号发送至的；另外，本数据分析还确认了ATF4是里面枢线粒体诱导引起则有口内素压制过程里面的不可或缺介导生物体。

本数据分析洞察了里面枢中枢神经系统ATF4在糖代谢全面性的插件，为数据分析里面枢恒定则有口内真诚提供了一个新的前景，并拓宽了里面枢线粒体诱导对胰脏口内素压制的数据分析，丰富了人们对各个骨髓的相互作用介导糖代谢的认识，借以随之而来人们对冠心病及具体的代谢功能性疾病发生前提的思考。

该项工作受益国家科技进步奖、科技部以及里面科院等工程技术基金的支持。

与中枢神经系统具体的拓展阅读：

doi:10.2337/db12-1050PMC:PMID:

Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve

Qian Zhang, Junjie Yu, Bin Liu, Ziquan Lv, Tingting Xia, Fei Xiao, Shanghai Chen and Feifan Guo*

Recent studies he revealed that the central nervous system (CNS), particularly the hypothalamus, is critical for regulating insulin sensitivity in peripheral tissues. The aim of our current study is to investigate the possible involvement of hypothalamic Activating Transcription Factor (ATF) 4 in the regulation of insulin sensitivity in the liver. Here, we show that overexpression of ATF4 in the hypothalamus resulting from intrentricular (icv) injection of adenovirus expressing ATF4 induces hepatic insulin resistance in mice and that inhibition of hypothalamic ATF4 by icv adenovirus expressing a dominant-negative ATF4 variant has the opposite effect. We also show that hypothalamic ATF4-induced insulin resistance is significantly blocked by selective hepatic vagotomy or by inhibiting activity of the mammalian target of rapamycin (mTOR) downstream target S6K1. Finally, we show that inhibition of hypothalamic ATF4 reverses hepatic insulin resistance induced by acute brain endoplasmic reticulum (ER) stress. Taken together, our study describes a novel central pathway regulating hepatic insulin sensitivity that is mediated by hypothalamic ATF4/mTOR/S6K1 signaling and the vagus nerve, and demonstrate an important role for hypothalamic ATF4 in brain ER stress-induced hepatic insulin resistance. These results may lead to the identification of novel therapeutic targets for treating insulin resistance and associated metabolic diseases.