Diabetes：郭非凡等揭示下丘脑ATF4调控肝脏胰岛感性的插件

近日，国际学术期刊Diabetes在线发表了里面科院汉口生科院营养成分科学研究课题所郭非凡四组的研究课题论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该研究课题详述了激素活化启动时表征4 (ATF4) 通过启动时细胞核S6K蛋白激酶(p70 S6K1)，进而诱导肺脏肝的肾脏理智的分子机制，洞察了激素ATF4适度肺脏人体内稳态的新功能。

2型式冠心病是一种慢性人体内性哮喘，随着穷困总体的愈发提高，我国2型式冠心病的发病率急速增大。以外关于2型式冠心病的研究课题主要集里面在肝等单个人体器官，而各个人体器官的交互作用对2型式冠心病影响的研究课题很少。周围神经，尤其是激素，在机体肺脏秘密四组织的肾脏理智适度里面起非常关键的作用，近年来已愈发已是一个研究课题热点。ATF4是CREB家族里面的一个关键核心人物，之前关于ATF4依赖性人体内的功能研究课题主要集里面在肺脏秘密四组织，例如ATF4 全身敲除小鼠会贫血，糖类下降，能量消耗增大，肾脏理智升高；成骨细胞里面免疫敲除ATF4也会提高肾脏理智等。但是周围神经里面ATF4确实参与肺脏肾脏理智的适度已确定引述。

郭非凡研究课题四组的博士生张倩等人辨认出，通过第三腹膜注射腺病毒介导的ATF4过表达尽可能引起肝的肾脏素抵御，而显性突变ATF4（dominant negative-ATF4）尽可能提高肝肾脏理智；进一步研究课题属实ATF4对肺脏糖人体内的适度是通过激素S6K1以及肝迷走神经信号传输的；另外，本研究课题还属实了ATF4是行政机构内质网凋亡引起肺脏肾脏素抵御更进一步里面的关键依赖性表征。

本研究课题洞察了行政机构激素ATF4在糖人体内不足之处的新功能，为研究课题行政机构适度肺脏肾脏理智获取了一个新的充满信心，并拓宽了行政机构内质网凋亡对肝肾脏素抵御的研究课题，丰富了人们对各个人体器官的交互作用依赖性糖人体内的认识，有助于加深人们对冠心病及之外的人体内性哮喘发生机制的理解。

该项指导得到重大项目、科技部以及里面科院等科研基金的支持。

与激素之外的持续发展阅读：

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.