NEUROPEPTIDE Y AND ITS ROLE IN CONGENITAL OBESITY

神经肽 Y 及其在先天性肥胖中的作用

• 批准号: 3245552
• 负责人: IAN L TAYLOR
• 金额: $ 14.24万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-15 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3245552
• 关键词: adrenal glands; adrenalectomy; adrenocorticotropic hormone; amygdala; appetite regulatory center; autoradiography; corticosterone; corticotropin releasing factor; crosslink; eating; epinephrine; gene expression; genetic strain; hormone regulation /control mechanism; hypothalamic pituitary axis; in situ hybridization; laboratory mouse; laboratory rat; median eminence; membrane reconstitution /synthesis; messenger RNA; neuropeptide Y; neuropeptide receptor; nutrition related tag; obesity; pancreatic polypeptide; paraventricular nucleus; radioimmunoassay; receptor binding; synaptosomes; tissue /cell culture

When injected into the cerebral ventricular or paraventricular nucleus (PVN), Neuropeptide Y (NPY) is the most potent stimulant of food intake known. It also stimulates the release of corticotropin releasing hormone (CRH), ACTH and cortisol. This latter action is dose dependent and shared by the structurally related peptide, pancreatic polypeptide (PP). NPY nerves that influence the PVN arise from the Nucleus Tractus Solitarius in the dorsal vagal comples and the amygdala. Bilateral destruction of the amygdala results in anorexia and weight loss in experimental animals. We propose 1) to compare NPY contents and NPY mRNA levels in that amygdala and PVN of obese and lean rats, 2) examine NPY binding in the hippocampus and PVN of obese and lean rats and mice, 3) examine structure-function requirements fro binding to these regions of the brain, 4) crosslink and characterize these receptor populations in obese and lean animals, 5) contrast NPY's ability to stimulate the release of CRH in obese and lean animals. These studies will be performed in male and female rats. Adrenalectomy abolishes the ability of NPY to stimulate food intake suggesting a relationship between the NPY's ability to stimulate food intake and the HPA axis. Congenital obese rodents, particularly males, exhiit a hyperactive hypothalamic- pituitary-adrenal axis (HPA) and adrenalectomy reverse the obesity in congenitally obese rodents. We will determine the effects of adrenalectomy and steroid supplementation on NPY contents in the amygdala and PVN and NPY binding to the hippocampus and PVN in Sprague Dawley rats. Similar studies will be repeated in obese rats. In prior studies we have established that ob/ob mice fail to release PP in response to a meal, a characteristic thay share with Prader-Willi children. Treatment with bovine PP is the only other treatment, other than adrenalectomy, that reverse the obesity and diabetes seen in these animals . Using autoradiography will have identified novel PP receptor populations in the brain (NTS) and adrenal that may mediate these beneficial effects. We will contrast bbinding of PP to the NTS in bese and lean rats and mice. We will also characterize the PP receptor population in the Zona Fasiculata and determine if PP inhibits corticosterone release. NPY and PP are structurally related peptides that are capable of modifying feeding behaviors and/or the HPA axis. These studies will clarify how these structurally related brain-gut peptides interact to control body weight.

当注射到脑室或旁脑室核中时 （PVN），神经肽Y（NPY）是食物摄入量最有效的兴奋剂 已知。 它还刺激皮质激素释放的释放 激素（CRH），ACTH和皮质醇。 后一种动作取决于剂量 并由结构相关的肽，胰多肽共享 （pp）。 影响PVN的NPY神经是由细胞核引起的 背面迷走神经的索利他里乌斯和杏仁核。 双边 杏仁核的破坏会导致厌食症和体重减轻 实验动物。 我们建议1）比较NPY内容和NPY 肥胖和瘦大鼠的杏仁核和PVN中的mRNA水平，2）检查 肥胖大鼠和小鼠的海马和PVN中的NPY结合， 3）检查与这些区域的结构功能要求 大脑，4）交联和表征这些受体人群 在肥胖和瘦动物中，5）对比NPY刺激的能力 在肥胖和瘦动物中释放CRH。 这些研究将是 在雄性和雌性大鼠中进行。 肾上腺切除术废除了能力 npy刺激食物摄入量，表明 NPY刺激食物摄入量和HPA轴的能力。 先天性 肥胖的啮齿动物，尤其是雄性，为下丘脑 - 垂体 - 肾上腺轴（HPA）和肾上腺切除术反转肥胖 先天肥胖的啮齿动物。 我们将确定 NPY含量的肾上腺切除术和类固醇补充剂 杏仁核和PVN和NPY结合与海马和Sprague中的PVN 道利老鼠。 肥胖大鼠将重复类似的研究。 在先验 研究我们已经确定OB/OB小鼠未能释放PP 对一顿饭的反应，与prader-willi的特征性分享 孩子们。 用牛PP治疗是唯一的其他治疗方法 比肾上腺切除术，扭转了肥胖和糖尿病 动物 。 使用放射自显影将确定新颖的PP受体 大脑中的种群（NTS）和肾上腺可能介导这些 有益的效果。 我们将对比PP与BESE的NTS进行对比 还有瘦的老鼠和老鼠。 我们还将表征PP受体 Zona Fasiculata中的人口并确定PP是否抑制 皮质酮释放。 NPY和PP是结构相关的肽 能够修改喂养行为和/或HPA轴的能力。 这些研究将阐明这些与结构相关的大脑脉 肽相互作用以控制体重。