Diabetes：郭非凡等揭示下丘脑ATF4调控消化系统胰岛感性的新功能

亦同，该协会学术期刊Diabetes在线发表了里面科院上海生科院营养科学科学研究所李非凡组的科学研究期刊“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该科学研究详述了神经递质活化激活因子4 (ATF4) 通过酪氨酸核糖体S6K蛋白激酶(p70 S6K1)，进而抑制锥体骨髓的胰脏理智的分子前提，洞察了神经递质ATF4缓冲锥体代谢周期性的补丁。

2型癌症是一种慢性代谢性病症，随着生活习惯水平的越来越大大提高，我国2型癌症的生育率急速减低。目前关于2型癌症的科学研究主要集里面在骨髓等单个骨髓，而各个骨髓的相互作用对2型癌症影响的科学研究大多。周围神经，众所周知是神经递质，在RX-锥体组织的胰脏理智缓冲里面起非常最重要的作用，近年来已逐渐成为一个科学研究同类型。ATF4是CREB家族里面的一个最重要核心人物，之前关于ATF4调节代谢的新功能科学研究主要集里面在锥体组织，例如ATF4 全身敲除小鼠亦会性病症，脂肪减低，能量消耗减低，胰脏理智升高；成骨细胞里面特异性敲除ATF4也亦会大大提高胰脏理智等。但是周围神经里面ATF4有否策划锥体胰脏理智的缓冲尚无华盛顿邮报。

李非凡科学研究团队的博士生张倩等人见到，通过第三腹腔麻醉腺病毒依赖性的ATF4过表达只能导致骨髓的胰脏素抵抗，而显性突变ATF4（dominant negative-ATF4）只能大大提高骨髓胰脏理智；全面科学研究证实ATF4对锥体糖代谢的缓冲是通过神经递质S6K1以及骨髓迷走神经信号传递的；另外，本科学研究还证实了ATF4是里面枢细胞内神经细胞导致锥体胰脏素抵抗处理过程里面的不可或缺调节因子。

本科学研究洞察了里面枢神经递质ATF4在糖代谢方面的补丁，为科学研究里面枢缓冲锥体胰脏理智提供了一个新的前景，并改建了里面枢细胞内神经细胞对骨髓胰脏素抵抗的科学研究，丰富了人们对各个骨髓的相互作用调节糖代谢的相识，有助于随之而来人们对癌症及相关的代谢性病症发生前提的理解。

该项工作得到国家自然科学基金会、国家科委以及里面科院等科研机构基金会的支持。

与神经递质相关的扩充阅读：

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.