title: Identification of nesfatin-1 as a satiety molecule in the hypothalamus.
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.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi 371-8511, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Oh-I
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Sachika
authors.initials: S
authors.lastname: Adachi
authors.forename: Kinji
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Imaki
authors.forename: Koushi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Monden
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling; D007031:Hypothalamus / Q000378:metabolism*; D007276:Injections, Intraventricular; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000494:pharmacology; D000080866:Nucleobindins; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D044101:Receptors, Melanocortin / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D044101:Receptors, Melanocortin; D000521:alpha-MSH