| Project/Area Number |
20591040
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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 |
Metabolomics
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| Research Institution | Tohoku University |
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Principal Investigator |
NONOGAKI Katunori Tohoku University, 未来医工学治療開発センター, 教授 (60370988)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 代謝 / 加齢 / 絶食 / 体重 / 脂肪 / Social Isolation / グレリン / エンドルフィン / SGK1 |
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| Research Abstract |
Social isolation enhanced fasting-induced weight loss and suppressed weight gain induced by re-feeding for 6 days following a 24-h fast in prepubertal wild-type mice. Under the same housing condition, genetic deletion of beta-endorphin reduced the fasting-induced weight loss and enhanced the re-feeding-induced weight gain in prepubertal mice. These effects of social isolation or genetic deletion of beta-endorphin on these weight changes were attenuated and reversed in postpubertal mice. Moreover, genetic deletion of beta-endorphin attenuated these effects of social isolation on the catch-up weight gain in prepubertal mice and reversed them in postpubertal mice. Thus, social isolation, endogenous beta-endorphin, and age can be novel modulators for body weight changes induced by fasting and re-feeding in mice. Despite no changes in plasma des-acyl ghrelin and the expression of hypothalamic neuropeptide Y and proopiomelanocortin, plasma active ghrelin levels and the expression of hypothalamic SGK-1 were increased in the acute-isolated C57BL6J mice. Injection of SGK-1 small interfering RNA oligonucleotide into the third cerebral ventricle suppressed the acute social isolation-induced decreases in body weight and increases in plasma active ghrelin levels. Pretreatment with phentolamine significantly suppressed the decreases in body weight. These finding suggest that hypothalamic SGK-1 contributes to the isolation stress-induced body weight reductions and increases in plasma active ghrelin levels via, at least partly, altered central autonomic outflow in mice.
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