| Project/Area Number |
14570093
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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 |
General pharmacology
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
YAMADA Jun Kobe Pharmaceutical University, Associate Professor, 薬学部, 助教授 (40140412)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Yumi Kobe Pharmaceutical University, Lecturer, 薬学部, 講師 (50187671)
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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 |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | leptin / serotonin / nitric oxide / food intake / anorexia / insulin |
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| Research Abstract |
Leptin is an adipocytokine, released from adipose tissue. Leptin is a strong anorectic factor by acting the hypothalamus which control food intake. It is well known that mice deficient of leptin display a marked hyperphagia and obesity. However, mechanism of leptin-induced hypophagia is not yet clarified. In this research, the involvement of serotonin(5-HT) and nitric oxide(NO) in anorexia elicited by leptin in mice. The 5-HT depleter significantly suppressed leptin-induced hypophagia. The 5-HT2B/2C receptor antagonist also reduced anorexia induced by leptin. Therefore, the 5-HT2B/2C receptor activation is involved in leptin-induced hypophagia. We found that leptin did not change brain NOx levels in staraved mice, although leptin inhibited food intake. The serum leptin levels were elevated by pretreatment with the 5-HT precursor, 5-hydroxytryptophan(5-HTP). Hyperleptinemia by 5-HTP is antagonized by streptozotocin which deplets insulin. Furthermore, increases in serum leptin levels induced by 5-HTP are inhibited by the NO synthesis inhibitor. These results suggest that leptin secretion may be controlled by 5-HT and NO and that 5-HT and NO play a significant role in leptin-induced anorexia.
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