Diabetes：郭非凡等揭示下丘脑ATF4调控肝脏口内感性的新功能

近日，国际学术期刊Diabetes网络服务刊发了里科院汉口生科院营养科学分析所徐非凡组的分析论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该分析探究了本部神经活化转录因子4 (ATF4) 通过激活核酸S6K蛋白激酶(p70 S6K1)，进而诱导肺脏肾脏的口内坦率的分子的系统，揭示了本部神经ATF4调节肺脏代谢物稳态的新内容。

2型哮喘是一种慢特质代谢物特质传染病，随着生活技术水平的日益提高，必将2型哮喘的发病率急速增加。目前关于2型哮喘的分析主要集里在肾脏等单个器官，而各个器官的振荡对2型哮喘影响的分析很少。本部神经系统，特别是在是本部神经，在各部位肺脏组织的口内坦率调节里起非常关键性的作用，近年来已逐渐成为一个分析热点。ATF4是CREB后代里的一个关键性成员，此前关于ATF4基因表达代谢物的系统分析主要集里在肺脏组织，例如ATF4 下半身敲除小鼠会贫血，脂肪缩减，能量消耗增加，口内坦率下降；成骨细胞里特异特质敲除ATF4也会提高口内坦率等。但是本部神经系统里ATF4是否参与肺脏口内坦率的调节尚未有报道。

徐非凡分析组的博士生张倩等人发现，通过第三脑室注射腺病毒诱导的ATF4过表达能够造成了肾脏的口内素压制，而显特质凋亡ATF4（dominant negative-ATF4）能够提高肾脏口内坦率；进一步分析证实ATF4对肺脏糖代谢物的调节是通过本部神经S6K1以及肾脏迷走神经接收机传递的；另外，本分析还证实了ATF4是本部溶酶体非典型造成了肺脏口内素压制过程里的更为关键性基因表达因子。

本分析揭示了本部本部神经ATF4在糖代谢物方面的新内容，为分析本部调节肺脏口内坦率提供了一个新的前景，并整建了本部溶酶体非典型对肾脏口内素压制的分析，丰富了人们对各个器官的振荡基因表达糖代谢物的认识，有助于促成人们对哮喘及就其的代谢物特质传染病牵涉到的系统的了解。

该项社会活动得到学科建设、科技部以及里科院等科研基金的支持者。

与本部神经就其的扩张阅读：

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.