Document Detail

Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus.
MedLine Citation:
PMID:  20551287     Owner:  NLM     Status:  MEDLINE    
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.
Koji Toshinai; Hideki Yamaguchi; Haruaki Kageyama; Takashi Matsuo; Keiichi Koshinaka; Kazuki Sasaki; Seiji Shioda; Naoto Minamino; Masamitsu Nakazato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-15
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  299     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-26     Completed Date:  2010-10-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E394-401     Citation Subset:  IM    
Univ. of Miyazaki, Kiyotake, Japan.
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MeSH Terms
Body Temperature / physiology
Cross-Over Studies
Energy Metabolism / physiology
Feeding Behavior / physiology*
Hypothalamus, Middle / metabolism*
Intracellular Signaling Peptides and Proteins / metabolism*
Mice, Knockout
Motor Activity / physiology
Nerve Tissue Proteins / metabolism*
Neuropeptides / metabolism*
Oxygen Consumption / physiology
Rats, Wistar
Signal Transduction / physiology
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Nerve Tissue Proteins; 0/Neuropeptides; 0/neuroendocrine regulatory peptide-1, rat; 0/neuroendocrine regulatory peptide-2, rat; 0/orexins

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