Diabetes：郭非凡等揭示外周ATF4调控肝脏胰岛感性的新功能

近日，国际季刊Diabetes在线发表了里面科院上海生科院营养科学知识科学知识研究室郭非凡三组的科学知识研究学术著作“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该科学知识研究阐明了肺脏活化转录因子4 (ATF4) 通过激活线粒体S6K乙酰(p70 S6K1)，进而抑制肺脏胰脏的去甲真诚的分子程序，阐述了肺脏ATF4适度肺脏细胞内稳态的新功能。

2同型白血病是一种慢性细胞内性疾病，随着生活水平的愈发降低，法制2同型白血病的发病率急速降低。目前关于2同型白血病的科学知识研究主要集里面在胰脏等单个器官，而各个器官的交互作用对2同型白血病直接影响的科学知识研究甚少。里面枢神经系统，尤其是肺脏，在EVA肺脏三组织的去甲真诚适度里面起非常不可忽视的作用，近年来已逐渐成为一个科学知识研究热点。ATF4是CREB后代里面的一个不可忽视成员，之前关于ATF4转录细胞内的功能科学知识研究主要集里面在肺脏三组织，例如ATF4 身躯敲除小鼠就会贫血，脂肪下降，利用效率降低，去甲真诚上升；成骨细胞里面特异性敲除ATF4也就会降低去甲真诚等。但是里面枢神经系统里面ATF4是否参与肺脏去甲真诚的适度尚无报道。

郭非凡科学知识副所长的博士生张倩等人发现，通过第三脑室静脉注射腺病毒介导的ATF4过表达只能惹来胰脏的去甲素压制，而显性特异性ATF4（dominant negative-ATF4）只能降低胰脏去甲真诚；更进一步科学知识研究证实ATF4对肺脏糖细胞内的适度是通过肺脏S6K1以及胰脏迷走神经信号传导的；另外，本科学知识研究还证实了ATF4是里面枢核糖体生理反应惹来肺脏去甲素压制全过程里面的不可或缺转录因子。

本科学知识研究阐述了里面枢肺脏ATF4在糖细胞内方面的新功能，为科学知识研究里面枢适度肺脏去甲真诚获取了一个一新大环境，并新建了里面枢核糖体生理反应对胰脏去甲素压制的科学知识研究，丰富了人们对各个器官的交互作用转录糖细胞内的了解，有效地激化人们对白血病及无关的细胞内性疾病发生程序的理解。

该项工作得到国家自然科学知识私人机构、教育部以及里面科院等科研私人机构的支持者。

与肺脏无关的开拓阅读：

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.