The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Cardiovascular Disease Research Center of Shandong First Medical University, Central Hospital Affiliated to Shandong First Medical University, Shandong, China.
Cell Death Dis. 2021 Mar 4;12(3):236. doi: 10.1038/s41419-021-03514-0.
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 (HuR) 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 HuR mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN.
肝脏在脂质和葡萄糖代谢中发挥重要作用。在这里，我们展示了 RNA 调节蛋白人抗原 R (HuR) 在肝细胞脂肪变性和葡萄糖代谢中的作用。我们研究了正常饮食 (NCD) 和高脂肪饮食 (HFD) 喂养的小鼠肝脏中 HuR 的水平。HuR 在 HFD 喂养的小鼠肝脏中下调。与对照小鼠相比，肝特异性 HuR 敲除 (HuR) 小鼠表现出更严重的 HFD 诱导的肝脂肪变性，同时葡萄糖耐量增强。从机制上讲，HuR 可以与磷酸酶和张力蛋白同源物缺失的染色体 10 (PTEN) mRNA 3'非翻译区的腺苷酸尿苷丰富元件结合，导致 Pten mRNA 的稳定性增加；HuR 的基因敲低降低了 PTEN 的表达。最后，慢病毒过表达 PTEN 减轻了 HuR 小鼠体内肝脂肪变性的发展。总的来说，HuR 通过靶向 PTEN 来调节脂质和葡萄糖代谢。
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