OBJECTIVES This study aimed to explore the involvement of the ghrelin pathway from the arcuate nucleus (ARC) to the dorsal vagal complex (DVC) and to determine its role in the regulation of glycolipid metabolism. METHODS The protein and mRNA expression of ghrelin and growth hormone (GH) secretagogue receptor type 1a (GHSR-1a) were measured using immunohistochemistry and the polymerase chain reaction (PCR) method, respectively. Ghrelin fiber projections arising from the ARC and projecting into the DVC were investigated using retrograde tracing, combined with fluorescence immunohistochemical staining. The effects of electrical stimulation (ES) of the ARC on ghrelin-responsive, glucose-sensitive DVC neurons, glycolipid metabolism, and liver lipid enzymes were determined using electrical physiological method, biochemical analysis, quantitative real-time PCR (qRT-PCR) and Western blot analysis. RESULTS GHSR-1a was expressed in the DVC neurons. Ghrelin fibers originating from the ARC projected into the DVC. ES of the ARC-activated the ghrelin-responsive glucose-excited (GE) and glucose-inhibited (GI) neurons in the DVC. ES of the ARC significantly elevated the serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and glucose levels; it reduced the serum high-density lipoprotein (HDLC) and insulin levels. Moreover, ES of the ARC increased liver acetyl-CoA carboxylase-1 (ACC-1) and decreased carnitine palmitoyltransferase-1 (CPT-1) expression, resulting in lipid accumulation in the liver. All the aforementioned effects were partially blocked by pretreatment with the ghrelin receptor antagonist [D-Lys-3]-GHRP-6 in the DVC and were reduced by vagotomy. ES of the ARC increased agouti-related protein (AgRP)/neuropeptide Y (NPY) expression in the ARC and ghrelin expression in the DVC. CONCLUSION Ghrelin fiber projections arising from the ARC and projecting into the DVC play a role in the regulation of afferent glucose metabolism and glycolipid metabolism via the ghrelin receptor GHSR-1a in the DVC.

中文翻译：

---

Ghrelin 纤维从下丘脑弓状核投射到背侧迷走神经复合体和糖脂代谢的调节

目的 本研究旨在探讨从弓状核 (ARC) 到迷走神经背复合体 (DVC) 的生长素释放肽途径的参与，并确定其在调节糖脂代谢中的作用。方法 分别采用免疫组化和聚合酶链反应（PCR）方法检测ghrelin和生长激素（GH）促分泌素受体1a（GHSR-1a）的蛋白和mRNA表达。使用逆行追踪结合荧光免疫组织化学染色研究了由 ARC 产生并投射到 DVC 中的 Ghrelin 纤维投射。ARC 的电刺激 (ES) 对生长素释放肽反应性、葡萄糖敏感性 DVC 神经元、糖脂代谢和肝脏脂质酶的影响使用电生理学方法、生化分析、实时定量 PCR (qRT-PCR) 和蛋白质印迹分析。结果 GHSR-1a 在 DVC 神经元中表达。源自 ARC 的 Ghrelin 纤维投射到 DVC 中。ARC 的 ES 激活了 DVC 中的生长素释放肽反应性葡萄糖兴奋 (GE) 和葡萄糖抑制 (GI) 神经元。ARC的ES显着升高血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和葡萄糖水平；它降低了血清高密度脂蛋白 (HDLC) 和胰岛素水平。此外，ARC 的 ES 增加了肝脏乙酰辅酶 A 羧化酶-1 (ACC-1) 并降低了肉碱棕榈酰转移酶-1 (CPT-1) 的表达，导致肝脏中的脂质积累。所有上述作用都被 DVC 中的生长素释放肽受体拮抗剂 [D-Lys-3]-GHRP-6 预处理部分阻断，并通过迷走神经切断术减少。ARC 的 ES 增加了 ARC 中刺鼠相关蛋白 (AgRP)/神经肽 Y (NPY) 的表达和 DVC 中生长素释放肽的表达。结论 ARC 产生并投射到 DVC 的 Ghrelin 纤维投射通过 DVC 中的 ghrelin 受体 GHSR-1a 在调节传入葡萄糖代谢和糖脂代谢中起作用。