Orexin-A signaling in the paraventricular nucleus modulates spontaneous firing of glucose-sensitive neurons and promotes food intake via the NPY pathway in rats.

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.