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Please use this identifier to cite or link to this item: http://hdl.handle.net/10087/1254

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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