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It appears that a newly identified gene predisposes how much
we consume in
food via central nervous system networks.

Identification of nesfatin-1 as a satiety molecule in the
hypothalamus p709
Shinsuke Oh-I, Hiroyuki Shimizu, Tetsurou Satoh, Shuichi
Okada, Sachika
Adachi, Kinji Inoue, Hiroshi Eguchi, Masanori Yamamoto,
Toshihiro Imaki,
Koushi Hashimoto, Takafumi Tsuchiya, Tsuyoshi Monden,
Kazuhiko Horiguchi,
Masanobu Yamada and Masatomo Mori

Nature 443, 709-12 (12 October 2006) Published online 1
October 2006

The brain hypothalamus contains certain secreted
molecules that are
important in regulating feeding behaviour1, 2, 3. 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.
... We have identified a novel anorexigenic nesfatin
corresponding to
NUCB2 in the hypothalamus that produces a secreted fragment,
nesfatin-1. At
the carboxy terminus matching the nesfatin-2/3 fragment,
NUCB2 possesses
archetypal motifs, namely possible calcium-binding and
DNA-binding sites5,
6, 7. The C-terminal region also binds other molecules21.
However, the
present findings indicate that this C terminus is not
involved in feeding
regulation. In contrast, nesfatin-1 located in the N
terminus of NUCB2 was
indispensable to the induction of satiety, and conversion of
NUCB2 to
nesfatin-1 was essential to induce its activity in vivo. ...