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Mechanism of appetite regulating peptides

食欲调节肽的作用机制

基本信息

批准号：
16390271
负责人：
KOJIMA Masayasu
金额：
$ 7.74万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390271/
关键词：
ghrelin neuromedin U appetite regulation promoter NF-kappa B gonadotropin pituitary 炎症骨代謝

项目摘要

1, Regulation of the human ghrelin promoter activityTo examine the gene expression of ghrelin, a growth hormone-releasing and appetite-stimulating hormone produced by the stomach, we constructed human ghrelin promoter-reporter vectors and analyzed promoter activity. Ghrelin promoter activity was high in cultured cells that endogenously express ghrelin mRNA, such as TT or ECC10 cells, indicating that these cells contain the factors necessary for full expression of human ghrelin. The human ghrelin promoter contains both positive and negative regulatory elements. A transient decrease in promoter activity was observed following transfection of a reporter vector containing the -1600 fragment of the human ghrelin promoter into cultured cells. We examined the effect of several transcription factors on ghrelin promoter activity ; NF-kB suppressed, while Nkx2.2, a homeodomain-containing transcription factor important for ghrelin-producing cell development in the pancreas, activates promoter activity. Lipopolysaccharide (LPS) binds Toll-like receptor 4, whose downstream signaling activates NF-kB. As LPS suppresses ghrelin expression levels, LPS may suppress ghrelin gene expression by activating NF-kB.2, Regulation of gonadotropin secretion and puberty onset by neuromedin UNeuromedin U (NMU), an anorexigenic peptide, was originally isolated from porcine spinal cord in 1985. As NMU is abundant in the anterior pituitary gland, we investigated the effects of NMU on gonadotropin secretion. Both NMU and its receptors, NMUR1 and NMUR2, were expressed in the pituitary gland. NMU suppressed LH and FSH releases from rat anterior pituitary cells. Moreover, NMU-deficient mice exhibit an early onset of vaginal opening. The LHbeta/FSHbeta ratio, which is an index of puberty onset, is high in young NMU-deficient mice. These results indicate that NMU suppresses gonadotropin secretion and regulates the onset of puberty.

1、人ghrelin启动子活性的调控为了检测由胃产生的生长激素释放和食欲刺激激素ghrelin的基因表达，我们构建了人ghrelin启动子-报告基因载体并分析了启动子活性。生长素释放肽启动子活性在内源性表达生长素释放肽mRNA的培养细胞中高，如TT或ECC 10细胞，表明这些细胞含有人生长素释放肽完全表达所必需的因子。人ghrelin启动子含有正调控元件和负调控元件。在将含有人ghrelin启动子的-1600片段的报道载体转染到培养的细胞中后，观察到启动子活性的瞬时降低。我们研究了几种转录因子对生长素释放肽启动子活性的影响; NF-κ B抑制，而Nkx2.2，一种对胰腺中生长素释放肽产生细胞发育重要的含同源结构域的转录因子，激活启动子活性。脂多糖（LPS）结合Toll样受体4，其下游信号传导激活NF-κ B。由于LPS抑制生长素释放肽的表达水平，LPS可能通过激活NF-κ B抑制生长素释放肽基因的表达。2.神经介肽对促性腺激素分泌和青春期启动的调节神经介肽U（NMU），一种促性腺激素生成肽，最初于1985年从猪脊髓中分离。由于NMU在垂体前叶中含量丰富，我们研究了NMU对促性腺激素分泌的影响。NMU及其受体NMUR 1和NMUR 2在垂体中表达。NMU抑制大鼠垂体前叶细胞LH和FSH的释放。此外，NMU缺陷型小鼠表现出阴道开放的早期发作。LH β/FSH β比值是青春期开始的指标，在年轻的NMU缺陷小鼠中很高。这些结果表明，NMU抑制促性腺激素分泌和调节青春期的开始。

项目成果

期刊论文数量（37）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock

DOI：
10.1016/j.bbrc.2006.01.075
发表时间：
2006-03-24
期刊：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
影响因子：
3.1
作者：
Moriyama, M;Matsukawa, A;Kojima, M
通讯作者：
Kojima, M

The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells.

DOI：
10.1084/jem.20050248
发表时间：
2005-07-18
期刊：
JOURNAL OF EXPERIMENTAL MEDICINE
影响因子：
15.3
作者：
Moriyama, Maiko;Sato, Takahiro;Inoue, Hiromasa;Fukuyama, Satoru;Teranishi, Hitoshi;Kangawa, Kenji;Kano, Tatsuhiko;Yoshimura, Akihiko;Kojima, Masayasu
通讯作者：
Kojima, Masayasu

Maternal ghrelin plays an important role in rat fetal development during pregnancy