| Project/Area Number |
14571077
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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 |
SHIBASAKI Tamotsu Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (00147399)
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| Co-Investigator(Kenkyū-buntansha) |
OHATA Hisayuki Nippon Medical School, Lecturer, 医学部, 助手 (80256924)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | growth hormone secretagogue / ghrelin / ghrelin receptor / transgenic rat / brown adipose tissue / noradrenaline / uncoupling protein / microdialysis / 体脂肪 / エネルギー代謝調節 / 褐色脂肪細胞 / 成長ホルモン分泌 |
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| Research Abstract |
To clarify the role of growth hormone secretagogue receptor(GHSR), we created transgenic(Tg) rats expressing an antisense GHSR mRNA under the control of the promoter for tyrosine hydroxylase, thus selectively attenuating GHSR protein expression in the arcuate nucleus of the hypothalamus. Tg rats had lower body weight and less adipose tissue than did control rats. The stimulatory effect of GHS treatment on feeding was abolished although the amount of food intake/100 g body weight was not reduced in Tg rats. These findings suggest that GHSR is involved in the regulation of energy metabolism, Tg rats showed higher O2 consumption and CO2 production and higher body temperature. In response to high fat meal, an increase in adipose tissue was smaller in Tg rats than control rats. The level of UCP1 expression was higher in Tg rats than control rats. Ghrelin inhibited noradrenaline release in the brown adipose tissue when administered intracerebroventricularly to control rats while it induced no significant change in noradrenaline release in the brown adipose tissue of the Tg rats. These results suggest that GHSR is involved in the reduction of energy consumption through the suppression of sympathetic nervous system in the brown adipose tissue. It is also suggested that energy consumption is increased through the inhibition of ghrelin action in Tg rats, thus causing low adiposity.
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