Diabetes：郭非凡等揭示下丘脑ATF4调节肝脏胰岛感性的新功能

近日，国际学术论文Diabetes离线出版了里面科院上海生科院食物科学研究社会活动所郑非凡第一组的研究社会活动篇文章“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该研究社会活动阐述了神经系统活化转录因子4 (ATF4) 通过激活核糖体S6K蛋白激酶(p70 S6K1)，进而抑制则有脾脏的家兔理智的化学键程序，揭示了神经系统ATF4可调则有细胞内平衡状态的新功能。

2型号冠心病是一种慢官能细胞内官能疾病，随着生活水平的日益大大提高，必将2型号冠心病的生育率急速上升。目前关于2型号冠心病的研究社会活动主要比较大在脾脏等单个肾脏，而各个肾脏的引力对2型号冠心病影响的研究社会活动很少。里面枢神经系统，尤其是神经系统，在各部位则有第一组织的家兔理智可调里面起极其不可或缺的作用，近年来已逐渐带进一个研究社会活动近期。ATF4是CREB三兄弟里面的一个不可或缺成员，之后关于ATF4管控细胞内的功能研究社会活动主要比较大在则有第一组织，例如ATF4 浑身敲除人体内都会贫血，脂肪增大，利用效率上升，家兔理智升高；成骨细胞里面选择官能敲除ATF4也都会大大提高家兔理智等。但是里面枢神经系统里面ATF4应该加入则有家兔理智的可调尚无报道。

郑非凡研究社会活动第一组的博士生张倩等人发现，通过第三腹膜注射腺病毒介导的ATF4过表述需要引起脾脏的家兔素反抗，而显官能突变ATF4（dominant negative-ATF4）需要大大提高脾脏家兔理智；进一步研究社会活动确认ATF4对则有糖细胞内的可调是通过神经系统S6K1以及脾脏喉部信号传递的；另外，本研究社会活动还确认了ATF4是里面枢内质网应激引起则有家兔素反抗过程里面的关键管控因子。

本研究社会活动揭示了里面枢神经系统ATF4在糖细胞内方面的新功能，为研究社会活动里面枢可调则有家兔理智缺少了一个新的大环境，并增建了里面枢内质网应激对脾脏家兔素反抗的研究社会活动，多样化了人们对各个肾脏的引力管控糖细胞内的认识，适度助长人们对冠心病及相关的细胞内官能疾病发生程序的理解。

该项社会活动得到国家自然科学基金、科技部以及里面科院等科研机构基金的拥护。

与神经系统相关的拓展阅读：

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.