Fan Xin-Tong, Tian Zhao, Li Shi-Zhen, Zhai Ting, Liu Jun-Li, Wang Rui, Zhang Cai-Shun, Wang Liu-Xin, Yuan Jun-Hua, Zhou Yu, Dong Jing
Clinical Medicine Department, Medical College, Qingdao University, Qingdao, China.
Preventive Medicine Department, School of Public Health, Qingdao University, Qingdao, China.
Front Endocrinol (Lausanne). 2018 Oct 24;9:633. doi: 10.3389/fendo.2018.00633. eCollection 2018.
Studies of nesfatin-1 in glucose metabolism have become a topic of interest recently, however, the specific receptor for nesfatin-1 has not yet been identified. Some studies hinted at a connection between nesfatin-1 and the ghrelin receptor, growth hormone secretagogue receptor. Therefore, we aimed to study the role of GHSR in the glycemic effects of nesfatin-1 as well as its downstream pathways. We employed C57/BL6 mice (wild type and GHSR knockout mice) eating a normal chow diet and a high fat diet in this study, and the experimental technique included western blot, real-time PCR, immunofluorescence and ELISA. We found that in mice fed a normal chow diet (NCD), nesfatin-1 improved glucose tolerance, up-regulated AKT kinase (AKT) mRNA levels and phosphorylation and GLUT4 membrane translocation in skeletal muscle. These effects were blocked by co-injection of GHSR antagonist [D-Lys3]-GHRP-6 and were attenuated in GHSR knockout mice. In mice fed high-fat diet (HFD), nesfatin-1 not only exerted the effects observed in NCD mice, but also suppressed appetite and raised AKT levels in liver tissues that also required GHSR. Peripheral nesfatin-1 suppressed c-fos expression of GHSR immunoreactive neurons induced by fasting in hypothalamic nuclei, indicating that nesfatin-1 inhibited the activation of central GHSR. We concluded that the effects of nesfatin-1 on food intake and glucose metabolism were GHSR-dependent, and that the glycemic effect was associated with AKT and GLUT4. This study should stimulate further exploration of the nesfatin-1 receptor.
最近，关于nesfatin-1在葡萄糖代谢方面的研究已成为一个热门话题，然而，nesfatin-1的特异性受体尚未被确定。一些研究暗示nesfatin-1与胃饥饿素受体（生长激素促分泌素受体）之间存在联系。因此，我们旨在研究生长激素促分泌素受体（GHSR）在nesfatin-1的血糖效应及其下游通路中的作用。在本研究中，我们使用了食用正常饲料和高脂饲料的C57/BL6小鼠（野生型和GHSR基因敲除小鼠），实验技术包括蛋白质免疫印迹法、实时聚合酶链反应、免疫荧光和酶联免疫吸附测定。我们发现，在喂食正常饲料（NCD）的小鼠中，nesfatin-1改善了葡萄糖耐量，上调了骨骼肌中AKT激酶（AKT）的信使核糖核酸水平、磷酸化水平以及葡萄糖转运蛋白4（GLUT4）的膜转位。这些效应被共同注射GHSR拮抗剂[D-Lys3]-GHRP-6所阻断，并且在GHSR基因敲除小鼠中减弱。在喂食高脂饲料（HFD）的小鼠中，nesfatin-1不仅发挥了在NCD小鼠中观察到的效应，还抑制了食欲，并提高了肝脏组织中同样需要GHSR的AKT水平。外周的nesfatin-1抑制了下丘脑核团中由禁食诱导的GHSR免疫反应性神经元的c-fos表达，表明nesfatin-1抑制了中枢GHSR的激活。我们得出结论，nesfatin-1对食物摄入和葡萄糖代谢的影响依赖于GHSR，并且血糖效应与AKT和GLUT4相关。这项研究应会激发对nesfatin-1受体的进一步探索。
