Inputs and outputs of NPY and BDNF neurons in the hypothalamus and their implication in feeding and metabolic regulation

下丘脑 NPY 和 BDNF 神经元的输入和输出及其在摄食和代谢调节中的意义

• 批准号: 18390065
• 负责人: YADA Toshihiko
• 金额: $ 9.48万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390065/
• 关键词: feeding; glucose; NPY; BDNF; CRH; urocortin; ghrelin; leptin; 弓状核; NPYニューロン; Ca^<2+>; レぷちん; 室傍核

We analyzed the inputs and outputs of neuropeptide Y (NPY) neurons and brain-derived neurotrophic factor (BDNF) neurons. NPY neurons in the hypothalamic arcuate : nucleus (ARC) were activated by ghrelin and inhibited by leptin. Leptin, via PI3 kinase and PDE3 signaling pathway, counteracted the action of ghrelin in NPY neurons. The integration of the two hormones determined the activity of NPY neurons and the feeding behavior. GK rats, a model of type 2 diabetes, showed young-adult specific hyperphagia, which was caused by elevated expression of NPY mRNA in the ARC, suggesting the pathophysiological role of the ARC NPY neurons.Central injection of BDNF increased expression of corticotropin-releasing hormone (CRH) and urocortin in the paraventricular nucleus (PVN), and thereby inhibited feeding and enhanced energy expenditure via CRH-R2 receptors. A new anorectic peptide, nesfatin-1, was abundant in PVN and colocalized with CRH, suggesting that nesfatin-1 could serve as a regulator of BDNF-CRH system.

我们分析了神经肽Y（NPY）神经元和脑源性神经营养因子（BDNF）神经元的输入和输出。下丘脑弧形：核（ARC）中的NPY神经元被生长素蛋白激活，并被瘦素抑制。通过PI3激酶和PDE3信号通路，瘦素抵消了生长素蛋白在NPY神经元中的作用。两种激素的整合确定了NPY神经元的活性和进食行为。 GK大鼠是一种2型糖尿病的模型，显示出年轻特定的特定于女性心形，这是由NPY mRNA在ARC中的表达升高引起的，这表明ARC NPY神经元的病理生理作用。bdnf的中性注射bdnf增加了皮质激素抑制的表达增加激素（CRH）和尿道素核中的核（PVN）中，从而通过CRH-R2受体抑制了饲喂和增强的能量消耗。一种新的Anorectic肽Nesfatin-1在PVN中很丰富，并与CRH共定位，这表明Nesfatin-1可以用作BDNF-CRH系统的调节剂。

项目成果

Regulation of feeding and metabolism by adipose-brain axis and its cellular and molecular mechanisms

脂肪-脑轴对摄食和代谢的调节及其细胞分子机制

• 发表时间: 2007
• 期刊: Endocrinology & Diabetology
• 作者: Nakata;M
• 通讯作者: M

Young adult-specific hyperphagia in diabetic Goto-Kakizaki rats is associated with leptin resistance and elevation of neuropeptide Y mRNA in the arcuate nucleus

• DOI: 10.1111/j.1365-2826.2006.01470.x
• 发表时间: 2006-10-01
• 期刊: JOURNAL OF NEUROENDOCRINOLOGY
• 影响因子: 3.2
• 作者: Maekawa, F.;Fujiwara, K.;Yada, T.
• 通讯作者: Yada, T.

Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance

• DOI: 10.2337/db06-0878
• 发表时间: 2006-12-01
• 期刊: DIABETES
• 影响因子: 7.7
• 作者: Dezaki, Katsuya;Sone, Hideyuki;Yada, Toshihiko
• 通讯作者: Yada, Toshihiko

Immunohistochemical and electron-microscopis observation of β-cells in pancreatic islets of spontaneously diabetic Goto-Kakizaki rats

自发性糖尿病 Goto-Kakizaki 大鼠胰岛 β 细胞的免疫组织化学和电镜观察

• 发表时间: 2006
• 期刊: Med Mol Morphol 39
• 作者: Toriya;M;Fujiwara K;Nakata M;Dezaki K;Nakata M;Kondo D;Fujiwara K;Maekawa F;Kuramochi M;Nakata M;Maekawa F;Dezaki K;Momose K
• 通讯作者: Momose K

Hypothalamic NPY neurons integrate metabolic and visceral signals to regulate feeding and its dysfunction in diabetic GK rats

下丘脑 NPY 神经元整合代谢和内脏信号来调节糖尿病 GK 大鼠的进食及其功能障碍

• 发表时间: 2008
• 作者: Kaneko K;Fukuda H;Chuang VTG;Yamasaki K;Kawahara K;Nakayama H;Suenaga A;Maruyama T;Otagiri M;Tanemoto M;Yu Ishima;Yada T
• 通讯作者: Yada T