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Role of brain serotonin systems and ghrelin in the regulation of feeding behavior

大脑血清素系统和生长素释放肽在进食行为调节中的作用

基本信息

批准号：
16500256
负责人：
NONOGAKI Katsunori
金额：
$ 2.37万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500256/
关键词：
serotonin ghrelin appetite 5-HT2C receptor 5-HT1B receptor POMC CART SGK-1 摂食 NPY メラノコルチンフルボキサミン SSRI グルコース

项目摘要

Brain serotonin (5-hydroxytryptamine ; 5-HT) systems contribute to regulate eating behavior and energy homeostasis. 5-HT2C receptors and 5-HT1B receptors have been shown to mediate anorexic effects of 5-HT drugs such as d-fenfluramine, which stimulates 5-HT release and inhibits 5-HT reuptake, and m-chlorophenylpiperazine (mCPP), a 5-HT2C receptor agonist. Here we report that 24-h fasting increased the expression of hypothalamic 5-HT2C receptor and 5-HT1B receptor genes in association with increases in plasma active ghrelin levels compared with fed state in mice. Treatment with mCPP or fenfluramine significantly inhibited the increases in plasma active ghrelin levels. mCPP or fenfluramine significantly increased the expression of hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript genes while having no significant effects on the expression of hypothalamic neuropeptide Y, agouti- related protein and ghrelin genes. These results suggest that there is a nega … More tive feedback system between brain 5-HT systems and plasma active ghrelin levels in energy homeostasis in mice (BBRC 341:703,2006).Serum- and glucocorticoid-induced protein kinase (SGK) is a serine/threonine-specific protein kinase that is transcriptionally regulated by serum, glucorticoids, and mineral corticoids. Here, we report that fasting or obesity with hyperphagia increased hypothalamic SGK-1 gene expression. Hypothalamic SGK-1 mRNA levels were proportional to daily food intake and body weights in C57BL6J mice, KK mice, and KKA^y mice matched for age. Plasma des-acyl ghrelin, but not active ghrelin, levels were inversely proportional to daily food intake and body weights among these animals. Under conditions of increased energy usage such as fasting, hypothalamic SGK-1 gene expression and plasma des-acyl ghrelin levels were positively correlated while during conditions of increased energy storage, they were negatively correlated. These results suggest that hypothalamic SGK-1 gene is a novel candidate gene involving in energy homeostasis in mice (BBRC 344:696,2006). Less

脑血清素（5-羟色胺; 5-HT）系统有助于调节进食行为和能量稳态。5-HT 2C受体和5-HT 1B受体已被证明介导5-HT药物如d-芬氟拉明（其刺激5-HT释放并抑制5-HT再摄取）和间氯苯哌嗪（mCPP）（一种5-HT 2C受体激动剂）的兴奋作用。在这里，我们报告说，24小时禁食增加下丘脑5-HT 2C受体和5-HT 1B受体基因的表达与血浆中活性生长激素释放肽水平的增加相比，在小鼠进食状态。用mCPP或芬氟拉明治疗显著抑制血浆活性ghrelin水平的增加。mCPP或芬氟拉明显著增加下丘脑前阿黑皮素、可卡因和苯丙胺调节的转录基因的表达，而对下丘脑神经肽Y、agglutin-related蛋白和ghrelin基因的表达无显著影响。这些结果表明，有一个负 ...更多信息血清和糖皮质激素诱导的蛋白激酶（SGK）是一种丝氨酸/苏氨酸特异性蛋白激酶，由血清、糖皮质激素和矿物质皮质激素转录调节。在这里，我们报告说，禁食或肥胖与暴食增加下丘脑SGK-1基因的表达。在年龄匹配的C57 BL 6 J小鼠、KK小鼠和KKA-γ小鼠中，下丘脑SGK-1 mRNA水平与每日食物摄入量和体重成比例。在这些动物中，血浆去酰基生长素释放肽（而非活性生长素释放肽）水平与每日摄食量和体重成反比。在增加能量使用的条件下，如禁食，下丘脑SGK-1基因表达和血浆去酰基ghrelin水平呈正相关，而在增加能量储存的条件下，它们呈负相关。这些结果表明，下丘脑SGK-1基因是一个新的候选基因参与能量稳态在小鼠（BBRC 344：696，2006）。少