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

Author

Listed:
  • Zhuojun Zhang

    (Peking University Health Science Center)

  • Chen Zong

    (Peking University Health Science Center)

  • Mingyang Jiang

    (Nanjing University)

  • Han Hu

    (Peking University Health Science Center)

  • Xiaolei Cheng

    (Peking University Health Science Center)

  • Juhua Ni

    (Peking University Health Science Center)

  • Xia Yi

    (Peking University Health Science Center)

  • Bin Jiang

    (Peking University Health Science Center)

  • Feng Tian

    (Peking University Health Science Center)

  • Ming-Wen Chang

    (National Institutes of Health)

  • Wen Su

    (Shenzhen University Health Science Center)

  • Lijun Zhu

    (Zhejiang University)

  • Jinfan Li

    (Zhejiang University)

  • Xueping Xiang

    (Zhejiang University)

  • Congxiu Miao

    (Changzhi Medical College)

  • Myriam Gorospe

    (National Institutes of Health)

  • Rafael Cabo

    (National Institutes of Health)

  • Yali Dou

    (University of Michigan)

  • Zhenyu Ju

    (Jinan University)

  • Jichun Yang

    (Peking University Health Science Center)

  • Changtao Jiang

    (Peking University Health Science Center)

  • Zhongzhou Yang

    (Nanjing University)

  • Wengong Wang

    (Peking University Health Science Center)

Abstract

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.

Suggested Citation

  • 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 & Myria, 2020. "Hepatic HuR modulates lipid homeostasis in response to high-fat diet," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16918-x
    DOI: 10.1038/s41467-020-16918-x
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    Cited by:

    1. Yumeng Peng & Qiang Zeng & Luming Wan & Enhao Ma & Huilong Li & Xiaopan Yang & Yanhong Zhang & Linfei Huang & Haotian Lin & Jiangyue Feng & Yixin Xu & Jingfei Li & Muyi Liu & Jing Liu & Changqin Lin &, 2021. "GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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