Hepatic HuR modulates lipid homeostasis in response to high-fat diet
Hepatic HuR modulates lipid homeostasis in response to high-fat diet
复制标题
肝脏 HuR 调节脂质稳态以响应高脂肪饮食
DOI：
10.1038/s41467-020-16918-x
复制
发表时间：
2020-06
影响因子：
16.6
通讯作者：
Yang Zhongzhou
中科院分区：
文献类型：
--
作者：
Zhang Zhuojun;Zong Chen;Jiang Mingyang;Hu Han;Cheng Xiaolei;Ni Juhua;Yi Xia;Jiang Bin;Tian Feng;Chang Ming-Wen;Su Wen;Zhu Lijun;Li Jinfan;Xiang Xueping;Miao Congxiu;Gorospe Myriam;de Cabo Rafael;Dou Yali;Ju Zhenyu;Yang Jichun;Jiang Changtao;Yang Zhongzhou
脂质转运和ATP合成对于非酒精性脂肪性肝病（NAFLD）的进展至关重要，但其潜在机制在很大程度上尚不清楚。在这里，我们报告说，RNA结合蛋白HuR（ELAVL 1）与NAFLD相关的转录形成复合物。它与Apobpre-mRNA的内含子24、Uqcrb的3′UTR和NDUFB 6 mRNA的5′UTR结合，从而调节ApobmRNA的剪接以及UQCRB和NDUFB 6的翻译。肝细胞特异性HuR敲除可降低小鼠APOB、UQCRB和NDUFB 6的表达，减少肝脏脂质转运和ATP合成，加重高脂饮食（HFD）诱导的NAFLD。腺病毒介导的肝细胞中HuR的再表达挽救了HFD诱导的NAFLD中HuR敲除的效果。我们的研究结果强调了HuR在调节脂质转运和ATP合成中的关键作用。
Lipid transport and ATP synthesis are critical for the progression of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) forms complexes with NAFLD-relevant transcripts. It associates with intron 24 ofApobpre-mRNA, with the 3′UTR ofUqcrb, and with the 5′UTR ofNdufb6mRNA, thereby regulating the splicing ofApobmRNA and the translation of UQCRB and NDUFB6. Hepatocyte-specific HuR knockout reduces the expression of APOB, UQCRB, and NDUFB6 in mice, reducing liver lipid transport and ATP synthesis, and aggravating high-fat diet (HFD)-induced NAFLD. Adenovirus-mediated re-expression of HuR in hepatocytes rescues the effect of HuR knockout in HFD-induced NAFLD. Our findings highlight a critical role of HuR in regulating lipid transport and ATP synthesis.
登录
查看更多内容
影响因子：
13.5
作者：
M. Pérez-Carreras;P. del Hoyo;Miguel Ángel Martín;J. Rubio;Ana Martín;G. Castellano;F. Colina;
通讯作者：
M. Pérez-Carreras;P. del Hoyo;Miguel Ángel Martín;J. Rubio;Ana Martín;G. Castellano;F. Colina;
影响因子：
6.5
作者：
J. Weiss;Ling Yang;Z. Qu
通讯作者：
J. Weiss;Ling Yang;Z. Qu
影响因子：
4.6
作者：
Hirose M;Schilf P;Gupta Y;Zarse K;Künstner A;Fähnrich A;Busch H;Yin J;Wright MN;Ziegler A;Vallier M;Belheouane M;Baines JF;Tautz D;Johann K;Oelkrug R;Mittag J;Lehnert H;Othman A;Jöhren O;Schwaninger M;Prehn C;Adamski J;Shima K;Rupp J;Häsler R;Fuellen G;Köhling R;Ristow M;Ibrahim SM
通讯作者：
Ibrahim SM
影响因子：
4
作者：
Simone, Laura E.;Keene, Jack D.
通讯作者：
Keene, Jack D.
影响因子：
13.5
作者：
Fujita, Koji;Nozaki, Yuichi;Nakajima, Atsushi
通讯作者：
Nakajima, Atsushi