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。下丘脑弓状核（ARC）内的NPY神经元被ghrelin激活，被leptin抑制。Leptin通过PI 3激酶和PDE 3信号通路，对抗ghrelin对NPY神经元的作用。这两种激素的整合决定了NPY神经元的活性和摄食行为。2型糖尿病模型GK大鼠表现出明显的成年特异性摄食过多，这是由于ARC中NPY mRNA表达增加所致，提示ARC中NPY神经元的病理生理作用，中枢注射BDNF可通过CRH-R2受体增加室旁核（PVN）中促肾上腺皮质激素释放激素（CRH）和尿皮质素（urocortin）的表达，从而抑制摄食，增加能量消耗。一种新的厌食肽nesfatin-1在PVN中含量丰富，并与CRH共定位，提示nesfatin-1可能是BDNF-CRH系统的调节因子。

项目成果

Cannabinoids inhibit insulin secretion and cytosolic Ca2+ oscillation in islet β-cells via CB1 receptors

• DOI: 10.1016/j.regpep.2007.08.009
• 发表时间: 2008-01-10
• 期刊: REGULATORY PEPTIDES
• 作者: Nakata, Masanori;Yada, Toshihiko
• 通讯作者: Yada, Toshihiko

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

Resistin induces insulin resistance in pancreatic islets to impair glucose-induced insulin release

• DOI: 10.1016/j.bbrc.2006.12.134
• 发表时间: 2007-02-23
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Nakata, Masanori;Okada, Takashi;Yada, Toshihiko
• 通讯作者: Yada, Toshihiko