HuR promotes triglyceride synthesis and intestinal fat absorption

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the mechanisms underlying are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3’UTR of Dgat2 mRNA and the introns 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3’UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption. To investigate the function of HuR in intestinal fat absorption, we generated a conditional intestinal epithelium-specific HuR knockout (cKO) mouse. RNA was extracted from the proximal jejunum in HuR cKO and their wild-type (WT) littermates. We then performed gene expression profiling analysis using data obtained from RNA-seq of 5 WT and cKO mice. Comparative gene expression profiling analysis of RNA-seq data for cKO mice and its WT littermates.