Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN.
Mi TianJingjing WangShangming LiuXinyun LiJingyuan LiJianmin YangCheng ZhangWencheng ZhangPublished in: Cell death & disease (2021)
The liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat diet (HFD). HuR was downregulated in the livers of HFD-fed mice. Liver-specific HuR knockout (HuRLKO) mice showed exacerbated HFD-induced hepatic steatosis along with enhanced glucose tolerance as compared with control mice. Mechanistically, HuR could bind to the adenylate uridylate-rich elements of phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) mRNA 3' untranslated region, resulting in the increased stability of Pten mRNA; genetic knockdown of HuR decreased the expression of PTEN. Finally, lentiviral overexpression of PTEN alleviated the development of hepatic steatosis in HuRLKO mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN.
Keyphrases
- high fat diet
- binding protein
- high fat diet induced
- cell proliferation
- insulin resistance
- pi k akt
- adipose tissue
- endothelial cells
- transcription factor
- wild type
- metabolic syndrome
- poor prognosis
- type diabetes
- weight loss
- gene expression
- signaling pathway
- high glucose
- dna methylation
- genome wide
- copy number
- mass spectrometry
- fatty acid
- protein protein
- gene therapy
- atomic force microscopy