Hepatic HuR modulates lipid homeostasis in response to high-fat diet
On June 16, 2020, professor Zhongzhou Yang from model animal research center of Nanjing university co-authored with Wengong Wang from Peking university health science center published a paper titled Hepatic HuR modulates lipid homeostasis in response to high-fat diet on Nature communications.
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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-specifific 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 fifindings highlight a critical role of HuR in regulating lipid transport and ATP synthesis.