Diabetes：郭非凡等揭示副交感神经ATF4调控肝脏胰岛感性的新功能

近日，国际学术刊物Diabetes在线发表了中所科院上海生科院营养社但会科学学术研究所陈非凡组的学术研究论文“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该学术研究阐明了神经递质活化核糖体遗传物质4 (ATF4) 通过激活核酸S6K磷酸化(p70 S6K1)，进而抑制水肿肾脏的呼吸道真挚的小分子机制，揭示了神经递质ATF4适度水肿细胞内稳态的新功能。

2DF肝炎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，我国2DF肝炎的肾癌急速增加。目前关于2DF肝炎的学术研究主要集中所在肾脏等单个内脏，而各个内脏的振荡对2DF肝炎影响的学术研究很少。中所枢神经系统，尤其是神经递质，在MS水肿组织的呼吸道真挚适度中所起非常重要的作用，近年来已逐渐成为一个学术研究近期。ATF4是CREB家族中所的一个重要成员，以前关于ATF4调控细胞内的功能学术研究主要集中所在水肿组织，例如ATF4 全身敲除小鼠但会贫血，碳水化合物提高，能量消耗增加，呼吸道真挚上升时；成骨细胞中所特异官能敲除ATF4也但会大大提高呼吸道真挚等。但是中所枢神经系统中所ATF4是否参与水肿呼吸道真挚的适度尚无报道。

陈非凡学术该中心的硕士生张倩等人注意到，通过第三脑室注射腺病毒内皮细胞的ATF4过解读能够导致肾脏的呼吸道素抗击，而显官能基因突变ATF4（dominant negative-ATF4）能够大大提高肾脏呼吸道真挚；必要性学术研究证实ATF4对水肿糖细胞内的适度是通过神经递质S6K1以及肾脏迷走神经信号传播的；另外，本学术研究还证实了ATF4是中所枢细胞内应激导致水肿呼吸道素抗击全过程中所的关键调控遗传物质。

本学术研究揭示了中所枢神经递质ATF4在糖细胞内方面的新功能，为学术研究中所枢适度水肿呼吸道真挚提供了一个新的前景，并拓宽了中所枢细胞内应激对肾脏呼吸道素抗击的学术研究，丰沛了人们对各个内脏的振荡调控糖细胞内的认识，有效地激化人们对肝炎及就其的细胞内官能疾病再次发生机制的理解。

该项岗位得到国家自然社但会科学基金、科技部以及中所科院等科研基金的赞同。

与神经递质就其的拓展选读：

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.