Diabetes：郭非凡等揭示下丘脑ATF4调控肝脏去甲感性的新功能

近日，国际性学术期刊Diabetes在线公开发表了当中科院上海生科院营养科学知识研究管理工作所刘非凡组的研究管理工作文章“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该研究管理工作阐明了血清素增殖转录因子4 (ATF4) 通过激活核糖体S6K蛋白激酶(p70 S6K1)，进而抑制骨骼肌肾脏的肾脏真诚的分子选择性，阐述了血清素ATF4调控骨骼肌新陈代谢参量的新功能性。

2改型乳癌是一种慢性新陈代谢性哮喘，随着生活水平的日益进一步提高，今后2改型乳癌的生育率急速增大。目前关于2改型乳癌的研究管理工作主要分散在肾脏等单个内脏，而各个内脏的相互作用对2改型乳癌影响的研究管理工作很少。的当中央神经系统，尤其是血清素，在机体骨骼肌民间组织的肾脏真诚调控当中起非常举足轻重的作用，近年来已逐渐视为一个研究管理工作最近。ATF4是CREB后裔当中的一个举足轻重成员，之前关于ATF4调控新陈代谢的功能性研究管理工作主要分散在骨骼肌民间组织，例如ATF4 全身敲除小鼠会贫血，油脂减少，利用效率增大，肾脏真诚升高；成骨细胞当中特异性敲除ATF4也会进一步提高肾脏真诚等。但是的当中央神经系统当中ATF4是否参加骨骼肌肾脏真诚的调控尚待报道。

刘非凡副所长的博士生张倩等人发现，通过第三血管壁注射腺病毒介导的ATF4过隐含都能引起肾脏的肾脏素抵御，而显性突变ATF4（dominant negative-ATF4）都能进一步提高肾脏肾脏真诚；进一步研究管理工作证实ATF4对骨骼肌糖新陈代谢的调控是通过血清素S6K1以及肾脏迷走神经瞬时传递的；另外，本研究管理工作还证实了ATF4是的当中央液泡应激引起骨骼肌肾脏素抵御全过程当中的关键调控因子。

本研究管理工作阐述了的当中央血清素ATF4在糖新陈代谢全面性的新功能性，为研究管理工作的当中央调控骨骼肌肾脏真诚提供者了一个新的前景，并拓宽了的当中央液泡应激对肾脏肾脏素抵御的研究管理工作，丰富了人们对各个内脏的相互作用调控糖新陈代谢的认识到，有效地随之而来人们对乳癌及具体的新陈代谢性哮喘发生选择性的理解。

该项管理工作得到学科建设、当中华民国行政院以及当中科院等科研成果全额的支持。

与血清素具体的拓展阅读：

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.