2005 Fiscal Year Final Research Report Summary
Role of brain serotonin systems and ghrelin in the regulation of feeding behavior
| Project/Area Number |
16500256
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
NONOGAKI Katsunori Tohoku University, Graduate School of Medicine, COE Fellow, 大学院・医学系研究科, COEフェロー (60370988)
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| Co-Investigator(Kenkyū-buntansha) |
EZAKI Osamu National Institute of Heath and Nutrition, Division of Clinical Nutrition, Director, 生活習慣病研究部, 部長 (90191923)
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| Project Period (FY) |
2004 – 2005
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| Keywords | serotonin / ghrelin / appetite / 5-HT2C receptor / 5-HT1B receptor / POMC / CART / SGK-1 |
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| Research Abstract |
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
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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
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