Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China; Clinical Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Biochem Biophys Res Commun. 2019 Mar 26;511(1):73-78. doi: 10.1016/j.bbrc.2019.02.037. Epub 2019 Feb 13.
β Adrenergic receptors (βARs) are G protein-coupled receptors (GPCRs) that are expressed in major insulin target tissues. βARs play an important role in the regulation of lipid metabolism during aging; however, little is known about the significance of βARs in the pathogenesis of hepatic fat accumulation in high-fat diet (HFD) mice. This study aims to examine the role of βAR in the development of nonalcoholic fatty liver disease (NAFLD) induced by HFD and the underlying mechanisms. Surprisingly, we found that genetic deletion of βAR significantly increased the liver weight of mice fed a HFD for 20 weeks compared to that of wild-type (WT) mice. Moreover, genetic deletion of βAR could aggravate HFD-induced liver lipid accumulation and liver injury in mice. Mechanistically, we demonstrated that βAR deletion significantly activated PPARγ/CD36 signaling via inactivation of the cAMP response element-binding (CREB) protein to facilitate hepatocellular lipid deposition in HFD mice. Together, our results identify βAR as a plausible therapeutic target for preventing or treating NAFLD.
β肾上腺素能受体（βAR）是在主要胰岛素靶组织中表达的 G 蛋白偶联受体（GPCR）。βAR 在衰老过程中脂质代谢的调节中发挥重要作用；然而，关于βAR 在高脂肪饮食（HFD）小鼠肝脂肪堆积发病机制中的意义知之甚少。本研究旨在研究βAR 在 HFD 诱导的非酒精性脂肪性肝病（NAFLD）发展中的作用及其潜在机制。令人惊讶的是，我们发现，与野生型（WT）小鼠相比，βAR 基因缺失显著增加了高脂饮食喂养 20 周的小鼠的肝重。此外，βAR 缺失可加重 HFD 诱导的小鼠肝脂质蓄积和肝损伤。在机制上，我们证明，βAR 缺失通过失活 cAMP 反应元件结合（CREB）蛋白显著激活 PPARγ/CD36 信号通路，从而促进 HFD 小鼠肝细胞脂质沉积。总之，我们的结果确定βAR 是预防或治疗 NAFLD 的一个合理的治疗靶点。
