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，世界官能学术期刊Diabetes在线公开发表了当中科院上海生科院营养科学学术研究所郭非凡组的学术研究论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该学术研究阐述了神经递质活化转录位点4 (ATF4) 通过酪氨酸核糖体S6K蛋白激酶(p70 S6K1)，进而抑制则有胰脏的家兔情感的分子机制，阐述了神经递质ATF4调节则有激素稳态的新功能。

2型白血病是一种慢官能激素官能疾病，随着生活水平的日益降低，法制2型白血病的发病率急速缩减。目前关于2型白血病的学术研究主要集当中在胰脏等单个器官，而各个器官的耦合对2型白血病影响的学术研究很少。所在之处神经系统，尤其是神经递质，在RX-则有组织的家兔情感调节当中起非常不可或缺的作用，近年来已逐渐带进一个学术研究版块。ATF4是CREB家族当中的一个不可或缺成员，之前关于ATF4管控激素的功能学术研究主要集当中在则有组织，例如ATF4 全身敲除小鼠亦会贫血，脂肪酸减少，能量消耗缩减，家兔情感升高；成骨细胞当中特异官能敲除ATF4也亦会降低家兔情感等。但是所在之处神经系统当中ATF4是否参与则有家兔情感的调节尚无美联社。

郭非凡学术该当中心的博士生张倩等人辨认出，通过第三脑室施用腺病毒介导的ATF4过传达很难引发胰脏的本品抵御，而显官能基因型ATF4（dominant negative-ATF4）很难降低胰脏家兔情感；必要官能学术研究证实ATF4对则有糖激素的调节是通过神经递质S6K1以及胰脏迷走神经信号传递的；另外，本学术研究还证实了ATF4是所在之处内质网凋亡引发则有本品抵御过程当中的关键管控位点。

本学术研究阐述了所在之处神经递质ATF4在糖激素方面的新功能，为学术研究所在之处调节则有家兔情感提供了一个新的前途，并拓宽了所在之处内质网凋亡对胰脏本品抵御的学术研究，丰富了人们对各个器官的耦合管控糖激素的重新认识，借以加深人们对白血病及特别的激素官能疾病发生机制的理解。

该项工作得到国家自然科学信托基金、行政院国家科学委员会以及当中科院等科研信托基金的支持。

与神经递质特别的拓展阅读：

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.