Diabetes：郭非凡等揭示下丘脑ATF4调控血液胰岛感性的新功能

据悉，国际学术期刊Diabetes在线刊出了之国防科工委汉口生科院营养生物科学研究课题所郑非凡组的研究课题专著“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该研究课题阐述了神经系统再生转录因子4 (ATF4) 通过激活RNAS6K乙酰(p70 S6K1)，进而抑制上皮细胞消化系统的家兔知性的分子机制，阐述了神经系统ATF4可调上皮细胞代谢物稳态的补丁。

2同型心血管疾病是一种慢性代谢物性营养不良，随着生活准确度的日益提高，我国2同型心血管疾病的发病率急速减少。目前关于2同型心血管疾病的研究课题主要集之中在消化系统等单个人体器官，而各个人体器官的耦合对2同型心血管疾病影响的研究课题很少。之本部神经系统，尤其是神经系统，在本机上皮细胞民间组织的家兔知性可调之中起颇为不可或缺的起到，近年来已渐渐成为一个研究课题旅游者。ATF4是CREB后代之中的一个不可或缺成员，前关于ATF4转录代谢物的功能研究课题主要集之中在上皮细胞民间组织，例如ATF4 全身敲除激素则会贫血，脂肪降低，能源消耗减少，家兔知性下降；成骨细胞之中特异性敲除ATF4也则会提高家兔知性等。但是之本部神经系统之中ATF4是否直接参与上皮细胞家兔知性的可调尚不报道。

郑非凡研究课题组的博士生张倩等人发现，通过第三血管壁口服腺病毒介导的ATF4过表达出来能够激起消化系统的家兔素对抗，而显性突变ATF4（dominant negative-ATF4）能够提高消化系统家兔知性；全面性研究课题得出结论ATF4对上皮细胞糖代谢物的可调是通过神经系统S6K1以及消化系统血液循环信号传递的；另外，本研究课题还得出结论了ATF4是之本部核糖体应激激起上皮细胞家兔素对抗过程之中的关键转录因子。

本研究课题阐述了之本部神经系统ATF4在糖代谢物之外的补丁，为研究课题之本部可调上皮细胞家兔知性包括了一个最初期望，并扩宽了之本部核糖体应激对消化系统家兔素对抗的研究课题，丰富了人们对各个人体器官的耦合转录糖代谢物的认识，更进一步更深人们对心血管疾病及之外的代谢物性营养不良发生机制的理解。

该项工作给予国家自然生物科学全额、科技部以及之国防科工委等人才培养全额的支持。

与神经系统之外的扩大阅读：

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.