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300112 病態制御内科学 >
学術雑誌論文 >
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http://hdl.handle.net/10087/1254
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Title: | Identification of nesfatin-1 as a satiety molecule in the hypothalamus |
Other Titles: | 生理:視床下部に局在する食欲抑制分子であるネスファチン-1の発見 |
Authors: | Oh-I, Shinsuke Shimizu, Hiroyuki Satoh, Tetsurou Okada, Shuichi Adachi, Sachika Inoue, Kinji Eguchi, Hiroshi Yamamoto, Masanori Imaki, Toshihiro Hashimoto, Koushi Tsuchiya, Takafumi Monden, Tsuyoshi Horiguchi, Kazuhiko Yamada, Masanobu Mori, Masatomo |
Issue Date: | 12-Oct-2006 |
Publisher: | Nature Publishing Group |
Citation: | Nature. 443, 709-712 (2006) |
Abstract: | The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus. |
URI: | http://hdl.handle.net/10087/1254 |
ISSN: | 0028-0836 |
Appears in Collections: | 学術雑誌論文
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