NEUROPEPTIDE Y--EFFECTS ON ENERGY METABOLISM

神经肽 Y——对能量代谢的影响

• 批准号: 6076521
• 负责人: Charles J. Billington
• 金额: $ 6.3万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6076521
• 关键词: appetite; appetite regulatory center; bioenergetics; brain mapping; brain metabolism; endogenous opioid; fasting; hypothalamus; laboratory rat; neuropeptide Y; nutrient intake activity; nutrition related tag; obesity; paraventricular nucleus; regulatory gene; solitary tract nucleus; thermogenesis

The brain's critical role in regulating energy and fat balance has never been more apparent. Several recent developments (see (l)) have focused attention on brain regulatory systems: leptin, the product of the ob gene, appears to signal fat status to the brain; the tubby gene appears to code for a protein expressed in hypothalamus; and a new satiety- inducing neuroregulator GLP-1 and feeding stimulator, melanocyte- concentrating hormone have been found to work in hypothalamus. It is evident that abnormalities in brain regulatory mechanisms may be responsible for alterations in energy balance (obesity, anorexia, etc.) in animals and in humans. Neuropeptide Y (NPY) is the most potent known neuroregulator of appetite and can be used, as described herein, to functionally map one brain system regulating energy balance (appetite and energy metabolism), which in this proposal we will call the Neuropeptide Y-Coded Energy Management Network (NEMN). The goal of these investigations is to define the central organization of one brain system regulating energy balance (appetite and energy metabolism), which in this proposal we will call the Neuropeptide Y-Coded Energy Management Network (NEMN). Abnormalities and disturbances in NEMN regulatory mechanisms could be responsible for alterations in energy balance (obesity, anorexia, etc.) in animals and in humans. Neuropeptide Y (NPY) is the most potent known orexigenic agent. We will utilize NPY administration into the hypothalamic paraventricular nucleus as the primary tool to functionally map the circuitry of the NEMN. We hypothesize a distributed energy management network in the brain, which can be traced using the stimulus of NPY. OBJECTIVES: (1) Define the neuronal sites activated by NPY in hypothalamic paraventricular nucleus, opioids in nucleus of the solitary tract, and by food deprivation through examining site specific expression of the immediate early gene, c-fos; (2) Verify the functional efferent link between NPY activity in the PVN and opioidergic activity in the NTS: (3) Functionally define the next circuit projections for the NPY-Coded Energy Management Network, (4) Define the site of action and regulatory significance of serotonin blockade of NPY effects on energy metabolism.

大脑在调节能量和脂肪平衡方面的关键作用从未如此 变得更加明显。最近的一些进展（见 (l)）重点关注 关注大脑调节系统：瘦素，OB的产物 基因，似乎向大脑发出脂肪状态信号；矮胖基因出现 编码下丘脑表达的蛋白质；和新的饱腹感—— 诱导神经调节剂 GLP-1 和进食刺激剂、黑素细胞- 已发现浓缩激素在下丘脑起作用。这是 显然，大脑调节机制的异常可能是 负责能量平衡的改变（肥胖、厌食等） 在动物和人类中。 神经肽 Y (NPY) 是已知最有效的食欲神经调节剂 且如本文所述，可用于绘制一个大脑的功能图 调节能量平衡（食欲和能量代谢）的系统， 在本提案中，我们将神经肽 Y 编码能量管理称为 网络（NEMN）。 这些调查的目的是确定中央组织 调节能量平衡（食欲和能量）的一个大脑系统 代谢），在本提案中我们将其称为神经肽 Y 编码 能源管理网络（NEMN）。 NEMN 中的异常和干扰 监管机制可能是能源变化的原因 动物和人类的平衡（肥胖、厌食等）。神经肽 Y (NPY) 是已知最有效的食欲促进剂。我们将利用 NPY 给药至下丘脑室旁核 对 NEMN 电路进行功能映射的主要工具。我们 假设大脑中有一个分布式能量管理网络， 可以使用 NPY 的刺激来追踪。 目的：（1）定义 NPY 激活的神经元位点 下丘脑室旁核，孤立核中的阿片类药物 道，并通过检查位点特异性表达来剥夺食物 立即早期基因，c-fos； (2) 验证功能性传出信号 PVN 中的 NPY 活性与 NTS 中的阿片类药物活性之间的联系： (3) 在功能上定义 NPY 编码的下一个电路投影 能源管理网络，(4) 定义行动地点和监管 血清素阻断 NPY 对能量代谢影响的意义。