Hepatic HuR modulates lipid homeostasis in response to high-fat diet.

Hepatic HuR modulates lipid homeostasis in response to high-fat diet.

Nature communications (2020-06-18)

Zhuojun Zhang, Chen Zong, Mingyang Jiang, Han Hu, Xiaolei Cheng, Juhua Ni, Xia Yi, Bin Jiang, Feng Tian, Ming-Wen Chang, Wen Su, Lijun Zhu, Jinfan Li, Xueping Xiang, Congxiu Miao, Myriam Gorospe, Rafael de Cabo, Yali Dou, Zhenyu Ju, Jichun Yang, Changtao Jiang, Zhongzhou Yang, Wengong Wang

PMID32546794

摘要

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 of Apob pre-mRNA, with the 3'UTR of Uqcrb, and with the 5'UTR of Ndufb6 mRNA, thereby regulating the splicing of Apob mRNA 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.