Diabetes：郭非凡等揭示下丘脑ATF4调控肝脏胰岛感性的模组

亦同，国际季刊Diabetes该软件登载了钱学森上海生科院摄取科学数据分析机构郭非凡两组的数据分析论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该数据分析阐明了副交感神经激活转录因子4 (ATF4) 通过激活核糖体S6K蛋白激酶(p70 S6K1)，进而抑制向外肝脏的人体内真挚的分子机制，揭示了副交感神经ATF4闭环向外代谢二阶的新功能。

2型肝炎是一种慢性代谢性病因，随着生活高度的日益大幅提高，必先2型肝炎的肾癌急速增大。目前关于2型肝炎的数据分析主要以外在肝脏等单个器官，而各个器官的交互依赖性对2型肝炎冲击的数据分析相当多。行政机关神经系统，尤其是副交感神经，在机体向外秘密两组织的人体内真挚闭环中的起非常关键性的依赖性，近来已迅速被选为一个数据分析版块。ATF4是CREB堂兄弟中的的一个关键性核心成员，之前关于ATF4催化反应代谢的功能数据分析主要以外在向外秘密两组织，例如ATF4 全身敲除小鼠可能会贫血，脂肪提高，除此以外增大，人体内真挚升高；成骨细胞中的特异性敲除ATF4也可能会大幅提高人体内真挚等。但是行政机关神经系统中的ATF4是否投身于向外人体内真挚的闭环不得而知报道。

郭非凡副所长的博士生张倩等人发现，通过第三脑室注射腺病毒介导的ATF4过表达能够造成了肝脏的人体内素抵抗，而显性突变ATF4（dominant negative-ATF4）能够大幅提高肝脏人体内真挚；进一步数据分析证实ATF4官方周糖代谢的闭环是通过副交感神经S6K1以及肝脏迷走神经路径传递的；另外，本数据分析还证实了ATF4是行政机关内质网诱发造成了向外人体内素抵抗步骤中的的关键催化反应因子。

本数据分析揭示了行政机关副交感神经ATF4在糖代谢方面的新功能，为数据分析行政机关闭环向外人体内真挚给予了一个新的前景，并拓宽了行政机关内质网诱发对肝脏人体内素抵抗的数据分析，丰富了人们对各个器官的交互依赖性催化反应糖代谢的认识到，有利于促使人们对肝炎及系统性的代谢性病因时有发生机制的解释。

该项管理工作得到国家自然科学投资基金、科技部以及钱学森等科研成果投资基金的赞同。

与副交感神经系统性的扩展到读到：

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.