| Project/Area Number |
17590970
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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 |
Endocrinology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
KAMEGAI Jun Nippon Medical School, Graduate School of Medicine, Special Research Fellow, 大学院・医学研究科, 特別研究生 (20204638)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Shinya Nippon Medical School, Faculty of Medicine, Research Associate, 医学部, 助手 (30267132)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | obesity / growth hormone / hypothalamus / resistin / somatostatin / growth hormone releasing hoemone / neuropeptide Y (NPY) / Growth hormone-releasing hormone / 脂肪細胞 / 甲状腺ホルモン / Proopiomelanocortin(POMC) |
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| Research Abstract |
Adipocyte-secreted hormones act on the hypothalamus to regulate food intake and GH secretion. In the present study, we have examined the effects of resistin on food intake and on hypothalamic neuropeptide expression. While resistin administered (1 μg/rat) intracerebroventricularly (i.c.v.) to fed rats did not modify food intake, treatment with resistin significantly decreased food intake in fasted rats in association with suppressed hypothalamic neuropeptide Y (NPY) mRNA levels. NPY has been implicated in the feedback mechanism for GH secretion. We next examined the effects of resistin (1 μg/rat, i.c.v.) or saline on GH secretion in adult male rats. While central administration of resistin did not modify spontaneous GH secretion in normally fed rats, administration of resistin to 72-hr fasted rats partially reversed the inhibitory effect of fasting on the GH secretion as assessed by the area under the curve (3550.0 ± 370.0 ng/ml/6 hr) compared to vehicle-treated rats (1010.0 ± 170.0 ng/m1/6 hr, P < 0.01). Furthermore, NPY mRNA levels were suppressed in resistin-treated 72-hr fasted rats. In addition, hypothalamic GHRH mRNA levels did not change, and somatostatin (SS) mRNA levels in the perivenrticular nucleus were suppressed in resistin-treated 72-hr fasted rats with in situ hybridization. Resistin at doses of 0.1-10 nM (4 hr) did not alter GH secretion from rat pituitary cell cultures. Taken together, these results suggest that resistin inhibits food intake in association with suppression of NPY expression. These findings suggest a role for NPY and SS as mediators of resistin-induced GH secretion.
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