NEUROPEPTIDE Y--EFFECTS ON ENERGY METABOLISM

神经肽 Y——对能量代谢的影响

• 批准号: 2016366
• 负责人: Charles J. Billington
• 金额: $ 15.86万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-10 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2016366
• 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 变得更加明显。最近的几个事态发展(见(L))引起了关注 关注大脑调节系统：瘦素，肥胖的产物 基因，似乎向大脑发出脂肪状态的信号；胖乎乎的基因出现 编码一种在下丘脑表达的蛋白质；以及一种新的饱腹感- 诱导神经调节因子GLP-1和摄食刺激物黑素细胞- 已发现集中荷尔蒙对下丘脑起作用。它是 显然，大脑调节机制的异常可能是 对能量平衡的改变负责(肥胖、厌食症等) 在动物和人类身上。 神经肽Y(NPY)是已知的最有效的食欲神经调节因子 并且如这里所描述的，可以用来功能性地映射一个大脑 调节能量平衡(食欲和能量代谢)的系统， 在本提案中，我们将称为神经肽Y编码的能量管理 网络(NEMN)。 这些调查的目标是确定中央组织 调节能量平衡(食欲和能量)的一个大脑系统 新陈代谢)，在本方案中我们将其称为神经肽Y编码 能源管理网络(NEMN)。NEMN中的异常和扰动 调节机制可能会对能源的变化负责 平衡(肥胖、厌食症等)在动物和人类身上。神经肽 Y(NPY)是已知的最有效的增食剂。我们将利用NPY 下丘脑室旁核给药 从功能上映射NEMN电路的主要工具。我们 假设大脑中有一个分布式能量管理网络，它 可以利用神经肽Y的刺激来追踪。 目的：(1)明确神经肽Y激活的神经元部位。 下丘脑室旁核，孤束核内的阿片样物质 途径，并通过检测部位特异性表达来剥夺食物 即刻早期基因c-fos；(2)验证功能传出 下丘脑室旁核NPY活性与孤束核阿片能活动之间的联系： (3)从功能上定义NPY编码的下一个电路预测 能源管理网络，(4)确定行动地点和监管 5-羟色胺阻断NPY对能量代谢的影响