Diabetes：蔡非凡等揭示下丘脑ATF4调控肝脏胰岛感性的新功能

亦同，该协会学术期刊Diabetes在线发表了里科院上海生科院营养科学科学研究机构杨非凡组的科学研究论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该科学研究阐明了本部神经系统活化激活遗传物质4 (ATF4) 通过激活核糖体S6K乙酰(p70 S6K1)，进而抑制则有肾脏的肝细胞真挚的分子机制，揭示了本部神经系统ATF4抑制则有代谢稳态的模组。

2型哮喘是一种慢性代谢性传染病，随着日常生活水平的愈加大幅提高，我国2型哮喘的发病率急速大幅提高。目前关于2型哮喘的科学研究主要集里在肾脏等单个人体器官，而各个人体器官的带电粒子对2型哮喘负面影响的科学研究常常。本部神经系统，尤其是本部神经系统，在机体则有组织起来的肝细胞真挚抑制里起非常不可或缺的作用，近年来已逐渐成为一个科学研究近来。ATF4是CREB家族里的一个不可或缺新成员，之前关于ATF4抑制代谢的功用科学研究主要集里在则有组织起来，例如ATF4 全身敲除小鼠会病变，胆固醇减低，能量消耗大幅提高，肝细胞真挚升高；成骨细胞里特异性敲除ATF4也会大幅提高肝细胞真挚等。但是本部神经系统里ATF4有否参与则有肝细胞真挚的抑制尚无刊文。

杨非凡科学研究组的研究生张倩等人挖掘出，通过第三脑室药剂腺病毒内源性的ATF4过传达必须惹来肾脏的肝细胞素压制，而显性凋亡ATF4（dominant negative-ATF4）必须大幅提高肾脏肝细胞真挚；必要性科学研究推测ATF4对则有糖代谢的抑制是通过本部神经系统S6K1以及肾脏迷走神经信号传达的；另外，本科学研究还推测了ATF4是本部细胞质非典型惹来则有肝细胞素压制过程里的关键抑制遗传物质。

本科学研究揭示了本部本部神经系统ATF4在糖代谢方面的模组，为科学研究本部抑制则有肝细胞真挚发放了一个新的前景，并拓宽了本部细胞质非典型对肾脏肝细胞素压制的科学研究，非常丰富了人们对各个人体器官的带电粒子抑制糖代谢的相识，有助于助长人们对哮喘及关的的代谢性传染病发生机制的解释。

该项工作得到国家自然科学信托基金、里华民国行政院以及里科院等工程技术信托基金的拥护。

与本部神经系统关的的拓展学习者：

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.