Diabetes：郭非凡等揭示下丘脑ATF4调控肝脏去甲感性的新功能

亦同，国际文摘Diabetes在线发表了副所长上海生科院营养科学学术研究所郑非凡组的学术研究学术著作“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该学术研究阐明了神经系统活化转录生物体4 (ATF4) 通过激活RNAS6K蛋白激酶(p70 S6K1)，进而消除骨骼肌骨髓的人体内真挚的分子选择性，阐述了神经系统ATF4调控骨骼肌葡萄糖波形的新动态。

2M-糖尿病是一种慢性葡萄糖性癌症，随着社会生活技术水平的日益提升，今后2M-糖尿病的患病率急速提升。目前关于2M-糖尿病的学术研究主要集中所在骨髓等单个生殖器官，而各个生殖器官的作用力对2M-糖尿病影响的学术研究很少。所在之处神经系统，尤其是神经系统，在机体骨骼肌其组织的人体内真挚调控中所起极为重要的作用，近年来已逐渐成为一个学术研究热点。ATF4是CREB家系中所的一个重要领导者，之前关于ATF4调控葡萄糖的动态学术研究主要集中所在骨骼肌其组织，例如ATF4 全身敲除小鼠亦会贫血，脂肪缩减，单单提升，人体内真挚升高；成骨细胞中所特异性敲除ATF4也亦会提升人体内真挚等。但是所在之处神经系统中所ATF4是否积极参与骨骼肌人体内真挚的调控尚无报道。

郑非凡学术研究组的博士生张倩等人挖掘出，通过第三脑室注射腺病毒介导的ATF4过表达尽也许引发骨髓的人体内素压制，而显性凋亡ATF4（dominant negative-ATF4）尽也许提升骨髓人体内真挚；必要性学术研究证实ATF4对骨骼肌糖葡萄糖的调控是通过神经系统S6K1以及骨髓喉部接收机传递的；另外，本学术研究还证实了ATF4是所在之处内质网非典M-引发骨骼肌人体内素压制每一次中所的决定性调控生物体。

本学术研究阐述了所在之处神经系统ATF4在糖葡萄糖全面性的新动态，为学术研究所在之处调控骨骼肌人体内真挚提供了一个新的前景，并拓宽了所在之处内质网非典M-对骨髓人体内素压制的学术研究，多样了人们对各个生殖器官的作用力调控糖葡萄糖的认识，有助加深人们对糖尿病及之外的葡萄糖性癌症发生选择性的理解。

该项社亦会活动得到国家自然科学投资公司、中所华民国行政院以及副所长等科研投资公司的支持。

与神经系统之外的拓展阅读：

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.