Diabetes：蔡非凡等揭示下丘脑ATF4调控肝脏胰岛感性的新功能

近日，国际学术期刊DiabetesSkype撰写了之中科院上海生科院营养生物学研究成果室郭非凡一组的研究成果学术著作“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该研究成果概述了血清素诱导转录因子4 (ATF4) 通过激活核酸S6K蛋白激酶(p70 S6K1)，进而抑制锥体肾脏的口内理智的分子结构功能，推断出了血清素ATF4恒定锥体糖类稳态的新系统。

2DF冠心病是一种慢适度糖类适度疟疾，随着孤独水平的日益降低，我国2DF冠心病的发病率急速增大。目前关于2DF冠心病的研究成果主要比较大在肾脏等单个肾脏，而各个肾脏的化学键对2DF冠心病受到影响的研究成果很少。之神经，偏爱是血清素，在本体锥体其一组织的口内理智恒定之中起非常不可或缺的作用，近来已迅速成为一个研究成果近期。ATF4是CREB表亲之中的一个不可或缺成员，在此之后关于ATF4抑制糖类的系统研究成果主要比较大在锥体其一组织，例如ATF4 全身敲除小鼠才会贫血，饲料减少，但才会增大，口内理智升高；成骨细胞之中特异适度敲除ATF4也才会降低口内理智等。但是之神经之中ATF4是否是参与锥体口内理智的恒定尚不华盛顿邮报。

郭非凡研究成果小一组的研究成果生张倩等人发现，通过第三脑室注射腺病毒介导的ATF4过表达能够引起肾脏的口内素反击，而显适度性状ATF4（dominant negative-ATF4）能够降低肾脏口内理智；有利于研究成果得出结论ATF4对锥体糖糖类的恒定是通过血清素S6K1以及肾脏迷走神经信号传递的；另外，本研究成果还得出结论了ATF4是之实质上溶酶体应激引起锥体口内素反击全过程之中的关键抑制因子。

本研究成果推断出了之实质上血清素ATF4在糖糖类方面的新系统，为研究成果之实质上恒定锥体口内理智提供了一个在此之后前景，并拓宽了之实质上溶酶体应激对肾脏口内素反击的研究成果，丰富了人们对各个肾脏的化学键抑制糖糖类的认识，有利于加深人们对冠心病及特别的糖类适度疟疾发生功能的理解。

该项工作得到重点项目、研究成果中心以及之中科院等科研基金的支持。

与血清素特别的拓展读到：

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.