Qingdao University School of Basic Medical Sciences, Shandong, Qingdao, 266071, China.
Qingdao University School of Basic Medical Sciences, Shandong, Qingdao, 266071, China.
Biochem Biophys Res Commun. 2018 Oct 20;505(1):162-167. doi: 10.1016/j.bbrc.2018.09.091. Epub 2018 Sep 20.
Understanding the mechanisms regulating feeding is crucial to unraveling the pathogenesis of obesity. The study primary explored the effects of orexin-A and neuropeptide Y (NPY) signaling in the hypothalamic paraventricular nucleus (PVN) on feeding and glucose-sensitive (GS) neuron activity in rats. Microinjection of orexin-A into the PVN promoted feeding and modulated the spontaneous firing of GS neurons. Those effects were eliminated by pre-injection of the orexin-A receptor-1 (OX1R) antagonist SB-334867 and weaken by the NPY-1 receptor (NPY-1R) antagonist BMS-193885. After orexin-A administration into the PVN, the number of c-fos cells in the arcuate nucleus (ARC) was significantly higher than that in the group receiving normal saline. Furthermore, most cells exhibited co-expression of NPY and c-fos, indicating activation of NPY neurons in the ARC by PVN-administered orexin-A, which might be involved in feeding regulation. These findings indicate that orexin-A and NPY signaling in the PVN are essential to regulating GS neuronal excitability and feeding in rats.
了解调节进食的机制对于揭示肥胖症的发病机制至关重要。本研究主要探讨了下丘脑室旁核（PVN）中食欲素-A 和神经肽 Y（NPY）信号对大鼠进食和葡萄糖敏感（GS）神经元活性的影响。将食欲素-A 微注射到 PVN 中会促进进食并调节 GS 神经元的自发放电。这些作用可被食欲素-A 受体-1（OX1R）拮抗剂 SB-334867 预先注射消除，也可被 NPY-1 受体（NPY-1R）拮抗剂 BMS-193885 减弱。在 PVN 给予食欲素-A 后，弓状核（ARC）中的 c-fos 细胞数量明显高于生理盐水组。此外，大多数细胞表现出 NPY 和 c-fos 的共表达，表明 PVN 给予的食欲素-A 激活了 ARC 中的 NPY 神经元，这可能参与了进食的调节。这些发现表明，PVN 中的食欲素-A 和 NPY 信号对于调节大鼠 GS 神经元兴奋性和进食至关重要。
