1. Hepatic HuR modulates lipid homeostasis in response to high-fat diet
- Author
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Jinfan Li, Xueping Xiang, Zhenyu Ju, Zhuojun Zhang, Changtao Jiang, Lijun Zhu, Juhua Ni, Ming-Wen Chang, Han Hu, Myriam Gorospe, Xia Yi, Congxiu Miao, Wengong Wang, Xiaolei Cheng, Wen Su, Mingyang Jiang, Yali Dou, Chen Zong, Jichun Yang, Feng Tian, Zhongzhou Yang, Rafael de Cabo, and Bin Jiang
- Subjects
0301 basic medicine ,Male ,Apolipoprotein B ,Molecular biology ,General Physics and Astronomy ,ELAV-Like Protein 1 ,0302 clinical medicine ,Adenosine Triphosphate ,Non-alcoholic Fatty Liver Disease ,RNA Precursors ,Homeostasis ,lcsh:Science ,Mice, Knockout ,Multidisciplinary ,ATP synthase ,biology ,Molecular medicine ,Chemistry ,Fatty liver ,Cytochromes c ,Cell biology ,NDUFB6 ,Liver ,030220 oncology & carcinogenesis ,Apolipoprotein B-100 ,lipids (amino acids, peptides, and proteins) ,Science ,Diet, High-Fat ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Medical research ,medicine ,Animals ,Lipid Transport ,Electron Transport Complex I ,nutritional and metabolic diseases ,Lipid metabolism ,General Chemistry ,medicine.disease ,Lipid Metabolism ,UQCRB ,Mice, Inbred C57BL ,030104 developmental biology ,Electron Transport Chain Complex Proteins ,biology.protein ,lcsh:Q - 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., Human antigen R (HuR) is a RNA binding protein involved in the regulation of many cellular functions. Here the authors show that, hepatocyte specific deletion of HuR exacerbates high-fat diet-induced NAFLD in mice by regulating transcripts involved in lipid transport and ATP synthesis.
- Published
- 2020