CONTROL OF FEEDING BEHAVIOR--HEPATIC AFFERENT SIGNALING

进食行为的控制——肝脏传入信号传导

• 批准号: 6380197
• 负责人: Charles Christopher Horn
• 金额: $ 7.53万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380197
• 关键词: acetates; afferent nerve; electrical measurement; electrophysiology; intravenous administration; laboratory rat; liver metabolism; mannitol; neural transmission; nutrient intake activity; nutrition related tag; solitary tract nucleus; thiols

DESCRIPTION (adapted from the application) The overall objective of the proposed research is to determine the properties of neural pathways from the liver to the brain that control feeding behavior and energy balance. This project will determine the hepatic metabolic stimuli that activate vagal afferent fibers and brainstem neurons. During the career award, the candidate will learn neurophysiological techniques to record from the nervous system of the anesthetized rat; this training will advance the candidate's career goal to become an independent research scientist. Dr. Gary Schwartz, Cornell University, will provide training in the recording of vagal afferent nerve activity; the instruction will focus on the isolation of single units and stimulation of the hepatic branch of the vagus. Dr. Ralph Norgren, Pennsylvania State University, will train the candidate to record single units from the nucleus of the solitary tract (NTS; brainstem sensory relay nucleus for the vagus). Experiments will be conducted at the Monell Chemical Senses Center (Philadelphia, PA) with Dr. Mark Friedman, an expert in the metabolic control of food intake, as the primary mentor. Previous research indicates that the vagus nerve is the route of passage for signals that arise from liver metabolism to affect feeding. 2,5-anhydro-D-mannitol (2,5-AM) and mercaptoacetate (MA), are two metabolic inhibitors with different actions that stimulate feeding behavior. The effects of these metabolic inhibitors on feeding are blocked by vagotomy, which suggests a peripheral site of action for these inhibitors on feeding. In the current project 2,5-AM and MA will be infused into the portal vein to isolate the treatments to the liver, while electrophysiological recordings are done from the vagus nerve and the NTS. The effects of 2,5-A.M and MA on single unit afferent activity will be compared to determine if these treatments activate the same population of hepatic afferent fibers (and if this population is distinct from glucose-sensitive fibers). A comparison between up-stream portal vein infusion and adjacent liver infusion will determine the site of action for the effects of 2,5 -AM and MA. on vagal afferent activity. Results from this project may contribute to a better understanding of metabolic stimuli that are sensed by the nervous system, and may elucidate neural controls that are involved in obesity, anorexia, and diabetes.

描述（改编自应用程序） 拟议研究的总体目标是确定 从肝脏到大脑控制进食行为的神经通路 和能量平衡。这个项目将确定肝脏代谢刺激 激活迷走神经传入纤维和脑干神经元。在职业生涯中 获奖后，候选人将学习神经生理学技术， 麻醉大鼠的神经系统;这种训练将促进 候选人的职业目标是成为一名独立的研究科学家。加里医生 康奈尔大学的施瓦茨将提供记录迷走神经的培训， 传入神经活动;该指令将集中在单个的隔离 单位和迷走神经的肝分支的刺激。拉尔夫·诺格伦博士， 宾夕法尼亚州立大学，将培养考生记录单单元 从孤束核（NTS;脑干感觉中继核 对于迷走神经）。实验将在Monell Chemical Senses进行 中心（费城，宾夕法尼亚州）与马克弗里德曼博士，在代谢的专家 控制食物的摄入量，作为主要的导师。先前的研究表明， 迷走神经是来自肝脏的信号的通路 代谢影响摄食。2，5-脱水-D-甘露醇（2，5-AM）和 巯基乙酸（MA）是两种作用不同的代谢抑制剂， 刺激进食行为。这些代谢抑制剂对 进食被迷走神经切断术阻断，这表明， 这些抑制剂对进食的影响在目前的项目中，2，5-AM和MA将是 输注到门静脉中以将治疗隔离到肝脏， 从迷走神经和NTS进行电生理记录。的 将比较2，5-A.M和MA对单个单位传入活动的影响， 确定这些治疗是否激活了相同的肝传入神经 纤维（如果该群体与葡萄糖敏感性纤维不同）。一 门静脉上游灌注与邻近肝脏灌注的比较 将决定2，5-AM和MA的作用部位。迷走神经的 传入活动该项目的结果可能有助于更好地 了解神经系统所感知的代谢刺激，以及 可以阐明与肥胖、厌食和肥胖相关的神经控制， 糖尿病