Diabetes：李非凡等揭示下丘脑ATF4调控肝脏胰岛感性的新功能

亦同，International医学期刊Diabetes在线发表了之前科院汉口生科院营养科学研究课题所蔡非凡组的研究课题论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该研究课题阐明了神经系统活化mRNA因子4 (ATF4) 通过激活核糖体S6K蛋白激酶(p70 S6K1)，进而消除肺脏消化系统的口内情感的分子选择性，推断出了神经系统ATF4适度肺脏代谢稳态的补丁。

2同型心血管疾病是一种慢官能代谢官能疾病，随着生活技术水平的日益进一步提高，我国2同型心血管疾病的出生率急速减少。目前关于2同型心血管疾病的研究课题主要集之前在消化系统等单个器官，而各个器官的交互作用对2同型心血管疾病因素的研究课题并不多。的之前央神经系统，尤其是神经系统，在RX-肺脏许多组织的口内情感适度之前起相当最重要的作用，近几年来已慢慢视作一个研究课题热点。ATF4是CREB家族之前的一个最重要成员，之前关于ATF4调控代谢的特性研究课题主要集之前在肺脏许多组织，例如ATF4 全身敲除小鼠会疾病，脂肪减少，可用减少，口内情感升高；成骨细胞之前特异官能敲除ATF4也会进一步提高口内情感等。但是的之前央神经系统之前ATF4是否参与肺脏口内情感的适度不得而知媒体报道。

蔡非凡研究课题组的博士生张倩等人发现，通过第三腹膜注射腺病毒介导的ATF4过表达出来很难引起消化系统的口内素抵抗，而显官能突变ATF4（dominant negative-ATF4）很难进一步提高消化系统口内情感；进一步研究课题证实ATF4对肺脏糖代谢的适度是通过神经系统S6K1以及消化系统迷走神经信号传达的；另外，本研究课题还证实了ATF4是的之前央核糖体应激引起肺脏口内素抵抗过程之前的最重要调控因子。

本研究课题推断出了的之前央神经系统ATF4在糖代谢方面的补丁，为研究课题的之前央适度肺脏口内情感包括了一个新的期望，并新建了的之前央核糖体应激对消化系统口内素抵抗的研究课题，比较丰富了人们对各个器官的交互作用调控糖代谢的认识，借以促成人们对心血管疾病及涉及的代谢官能疾病发生选择性的理解。

该项工作得到国家自然科学私人机构、农业部以及之前科院等科研私人机构的支持。

与神经系统涉及的拓展阅读：

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.