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

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 3UTR 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.