Diabetes：郭非凡等阐释下丘脑ATF4调控肝脏胰岛感性的新功能

已对，国际期刊DiabetesSkype发表了中都科院上海生科院营养科学研究成果所郭非凡组的研究成果期刊“Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve”。该研究成果阐明了副交感神经活化转录系数4 (ATF4) 通过转录核糖体S6K蛋白激酶(p70 S6K1)，进而消除上皮细胞肝的口内真诚的分子的系统，了解到了副交感神经ATF4可调上皮细胞代谢稳态的新系统。

2M-乳癌是一种慢特质代谢特质病症，随着家庭低水平的大为提高，必将2M-乳癌的肾癌急速增加。目前关于2M-乳癌的研究成果主要密集在肝等单个人体器官，而各个人体器官的振荡对2M-乳癌影响的研究成果很少。中都枢神经系统，尤其是副交感神经，在机上皮细胞组织的口内真诚可调中都起非常极其重要的作用，近十年已不断成为一个研究成果热点。ATF4是CREB家族中都的一个极其重要团员，之前关于ATF4催化反应代谢的功能研究成果主要密集在上皮细胞组织，例如ATF4 全身敲除小鼠才会贫血，脂肪缩减，能源消耗增加，口内真诚升高；成骨细胞中都特异特质敲除ATF4也才会提高口内真诚等。但是中都枢神经系统中都ATF4是否参与上皮细胞口内真诚的可调已为报道。

郭非凡研究成果组的博士生张倩等人发现，通过第三脑室注射腺病毒介导的ATF4过传达只能引起肝的口内素抵挡，而显特质突变ATF4（dominant negative-ATF4）只能提高肝口内真诚；进一步研究成果证实ATF4对上皮细胞糖代谢的可调是通过副交感神经S6K1以及肝血液循环信号传递的；另外，本研究成果还证实了ATF4是中都枢内质网应激引起上皮细胞口内素抵挡全过程中都的这两项催化反应系数。

本研究成果了解到了中都枢副交感神经ATF4在糖代谢方面的新系统，为研究成果中都枢可调上皮细胞口内真诚缺少了一个原先前景，并拓宽了中都枢内质网应激对肝口内素抵挡的研究成果，珍贵了人们对各个人体器官的振荡催化反应糖代谢的交往，有效地加剧人们对乳癌及之外的代谢特质病症频发的系统的表达出来。

该项工作得到博士生、科技部以及中都科院等科研基金的赞成。

与副交感神经之外的拓展读到：

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.