PMID- 17036007
OWN - NLM
STAT- MEDLINE
DCOM- 20061109
LR  - 20220410
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 443
IP  - 7112
DP  - 2006 Oct 12
TI  - Identification of nesfatin-1 as a satiety molecule in the hypothalamus.
PG  - 709-12
AB  - 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.
FAU - Oh-I, Shinsuke
AU  - Oh-I S
AD  - Department of Medicine and Molecular Science, Gunma University Graduate School of 
      Medicine, Showa-machi, Maebashi 371-8511, Japan.
FAU - Shimizu, Hiroyuki
AU  - Shimizu H
FAU - Satoh, Tetsurou
AU  - Satoh T
FAU - Okada, Shuichi
AU  - Okada S
FAU - Adachi, Sachika
AU  - Adachi S
FAU - Inoue, Kinji
AU  - Inoue K
FAU - Eguchi, Hiroshi
AU  - Eguchi H
FAU - Yamamoto, Masanori
AU  - Yamamoto M
FAU - Imaki, Toshihiro
AU  - Imaki T
FAU - Hashimoto, Koushi
AU  - Hashimoto K
FAU - Tsuchiya, Takafumi
AU  - Tsuchiya T
FAU - Monden, Tsuyoshi
AU  - Monden T
FAU - Horiguchi, Kazuhiko
AU  - Horiguchi K
FAU - Yamada, Masanobu
AU  - Yamada M
FAU - Mori, Masatomo
AU  - Mori M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061001
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Leptin)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nucb1 protein, mouse)
RN  - 0 (Nucb1 protein, rat)
RN  - 0 (Nucleobindins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Leptin)
RN  - 0 (Receptors, Melanocortin)
RN  - 581-05-5 (alpha-MSH)
SB  - IM
MH  - Animals
MH  - Anorexia/chemically induced/metabolism/prevention & control
MH  - Appetite Regulation/drug effects/*physiology
MH  - Body Weight/drug effects
MH  - Calcium-Binding Proteins/administration & 
      dosage/chemistry/metabolism/pharmacology
MH  - DNA-Binding Proteins/administration & dosage/chemistry/metabolism/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Feeding Behavior/drug effects/*physiology
MH  - Gene Expression Profiling
MH  - Hypothalamus/*metabolism
MH  - Injections, Intraventricular
MH  - Leptin/metabolism/pharmacology
MH  - Male
MH  - Mice
MH  - Nerve Tissue Proteins/administration & dosage/cerebrospinal 
      fluid/*metabolism/pharmacology
MH  - Nucleobindins
MH  - Obesity/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Rats, Zucker
MH  - Receptors, Cell Surface/genetics/metabolism
MH  - Receptors, Leptin
MH  - Receptors, Melanocortin/metabolism
MH  - Satiety Response/drug effects/*physiology
MH  - Signal Transduction/drug effects
MH  - alpha-MSH/metabolism
EDAT- 2006/10/13 09:00
MHDA- 2006/11/11 09:00
CRDT- 2006/10/13 09:00
PHST- 2006/06/08 00:00 [received]
PHST- 2006/08/11 00:00 [accepted]
PHST- 2006/10/13 09:00 [pubmed]
PHST- 2006/11/11 09:00 [medline]
PHST- 2006/10/13 09:00 [entrez]
AID - nature05162 [pii]
AID - 10.1038/nature05162 [doi]
PST - ppublish
SO  - Nature. 2006 Oct 12;443(7112):709-12. doi: 10.1038/nature05162. Epub 2006 Oct 1.