BEHAVIORAL PHYSIOLOGY OF BODY WEIGHT REGULATION

体重调节的行为生理学

• 批准号: 3241477
• 负责人: DIANNE FIGLEWICZ LATTEMANN
• 金额: $ 16.65万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241477
• 关键词: animal age group; body weight; cerebral cortex; diacylglycerols; female; gender difference; growth /development; hippocampus; hormone regulation /control mechanism; hypothalamus; inositol; insulin; insulin receptor; ion exchange chromatography; laboratory rat; lipid metabolism; male; membrane lipids; neuroendocrine system; norepinephrine; nutrient intake activity; nutrition related tag; obesity; olfactory lobe; phospholipids; phosphorylation; protein kinase C; radioimmunoassay; receptor binding; thin layer chromatography; tritium; weight control

Studies have suggested that insulin may be a regulator of food intake and body weight by acting at the central nervous system (CNS). This renewal proposal addresses the hypothesis that the ability of insulin to act as a satiety signal may change during normal growth and development, and may be abnorrnal in obesity. Studies are proposed to examine whether insulin uptake into the CNS, or insulin action-in the CNS, is altered in rats as a function of age, gender, and genetic or diet-induced obesity. Insulin uptake by brain will be assessed in vivo by measurement of steady state levels of plasma and CSF insulin during vehicle or insulin infusions. Brain capillary insulin binding sites will be measured as an in vitro estimate of specific receptor-mediated transport capacity. Regulation of these receptors has been observed by this laboratory and others and may represent a potential mechanism for regulation of insulin uptake into the CNS. Insulin action will be assessed behaviorally by measuring body weight and food intake in response to intraventricular insulin infusions. Insulin action in vitro will be assessed by measurement of insulin effects on norepinephrine uptake and post-synaptic events in the hippocampus, a brain region in which I have demonstrated insulin stimulation of phospholipid metabolism which may be mediated locally by catecholamines, as well as in the hypothalamus and olfactory bulb, two brain regions which play a major role in the regulation of food intake and body weight, and compared with changes of peripheral insulin action. Together, these studies should determine whether the effectiveness of the candidate CNS adiposity signal, insulin, is regulated by changes in its uptake and/or action in the CNS.

研究表明，胰岛素可能是食物摄入量的调节器。 通过作用于中枢神经系统(CNS)来控制体重。这 更新建议解决了这样的假设，即胰岛素的能力 作为饱腹感的信号在正常生长和发育过程中可能会发生变化， 在肥胖方面可能是异常的。建议进行研究以检查 无论是胰岛素摄取到中枢神经系统，还是胰岛素在中枢神经系统的作用， 大鼠的年龄、性别和基因或基因的变化 饮食导致的肥胖。大脑对胰岛素的摄取将在体内进行评估 通过测定血浆和脑脊液中胰岛素的稳态水平 车辆或胰岛素输注。脑毛细血管胰岛素结合部位 将作为特定受体介导的体外估计进行测量 运输能力。这些受体的调节已经被观察到 该实验室和其他实验室，并可能代表一种潜在的机制 中枢神经系统对胰岛素摄取的调节。胰岛素的作用将是 通过测量体重和食物摄入量来评估行为 脑室注射胰岛素的反应。胰岛素的体外作用 将通过测量胰岛素对去甲肾上腺素的影响来进行评估 海马区的摄取和突触后事件 我已经证明了胰岛素对磷脂代谢的刺激 它可能由局部的儿茶酚胺介导，以及在 下丘脑和嗅球，这两个大脑区域发挥着重要的 在调节食物摄入量和体重方面的作用，并与 外周胰岛素作用的变化。总而言之，这些研究应该 确定候选中枢神经系统肥胖症的有效性 信号，胰岛素，是由其摄取和/或作用的变化来调节的 中枢神经系统。