PMID- 20551287
OWN - NLM
STAT- MEDLINE
DCOM- 20101006
LR  - 20151119
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 299
IP  - 3
DP  - 2010 Sep
TI  - Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin 
      system in the hypothalamus.
PG  - E394-401
LID - 10.1152/ajpendo.00768.2009 [doi]
AB  - Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 are derived from distinct 
      regions of VGF, a neurosecretory protein. Vgf(-/-) mice exhibit dwarfism and 
      hypermetabolic rates, suggesting that VGF or VGF-derived peptides play important 
      roles in energy metabolism. Here, we examined the role of NERPs in the central 
      regulation of feeding and energy homeostasis. We attempted to identify NERPs 
      expressing neurons in rats by immunohistochemistry. We studied the effects of 
      intracerebroventricular (icv) administration of NERP-2 on feeding, body 
      temperature, oxygen consumption, and locomotor activity in rats and mice. 
      Intracerebroventricular administration of NERP-2, but not NERP-1 or a form of 
      NERP-2 bearing a COOH-terminal glycine extension, increased food intake in rats. 
      We investigated the downstream signal of NERP-2 on the basis of studies of 
      NERP-2-induced feeding with neutralization of orexins, neuropeptide Y, or 
      agouti-related protein. NERP-2 expression localized to the lateral hypothalamus 
      (LH) and the dorsomedial perifornical hypothalamus in rats, colocalizing with 
      orexins that activate feeding behavior and arousal. NERP-2 administration induced 
      Fos protein, a marker of neuronal activation, in the orexin-immunoreactive 
      neurons. Vgf mRNA levels were upregulated in the rat LH upon food deprivation. 
      Intracerebroventricular administration of NERP-2 also increased body temperature, 
      oxygen consumption, and locomotor activity in rats. Treatment with anti-NERP-2 
      IgG decreased food intake. NERP-2-induced bioactivities could be abrogated by 
      administration of anti-orexins IgG or orexin receptor antagonists. NERP-2 did not 
      induce food intake or locomotor activity in orexin-deficient mice. Our findings 
      indicate that hypothalamic NERP-2 plays a role in the control of food intake and 
      energy homeostasis via the orexin pathway. Thus, VGF serves as a precursor of 
      multiple bioactive peptides exerting a diverse set of neuroendocrine functions.
FAU - Toshinai, Koji
AU  - Toshinai K
AD  - Univ. of Miyazaki, Kiyotake, Japan.
FAU - Yamaguchi, Hideki
AU  - Yamaguchi H
FAU - Kageyama, Haruaki
AU  - Kageyama H
FAU - Matsuo, Takashi
AU  - Matsuo T
FAU - Koshinaka, Keiichi
AU  - Koshinaka K
FAU - Sasaki, Kazuki
AU  - Sasaki K
FAU - Shioda, Seiji
AU  - Shioda S
FAU - Minamino, Naoto
AU  - Minamino N
FAU - Nakazato, Masamitsu
AU  - Nakazato M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100615
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexins)
RN  - 0 (neuroendocrine regulatory peptide-1, rat)
RN  - 0 (neuroendocrine regulatory peptide-2, rat)
SB  - IM
MH  - Animals
MH  - Body Temperature/physiology
MH  - Cross-Over Studies
MH  - Energy Metabolism/physiology
MH  - Feeding Behavior/*physiology
MH  - Hypothalamus, Middle/*metabolism
MH  - Immunohistochemistry
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity/physiology
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neuropeptides/*metabolism
MH  - Orexins
MH  - Oxygen Consumption/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/physiology
EDAT- 2010/06/17 06:00
MHDA- 2010/10/07 06:00
CRDT- 2010/06/17 06:00
PHST- 2010/06/17 06:00 [entrez]
PHST- 2010/06/17 06:00 [pubmed]
PHST- 2010/10/07 06:00 [medline]
AID - ajpendo.00768.2009 [pii]
AID - 10.1152/ajpendo.00768.2009 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E394-401. doi: 
      10.1152/ajpendo.00768.2009. Epub 2010 Jun 15.