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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-8-26
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1522-1555
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E394-401
pubmed:meshHeading
pubmed-meshheading:20551287-Animals, pubmed-meshheading:20551287-Body Temperature, pubmed-meshheading:20551287-Cross-Over Studies, pubmed-meshheading:20551287-Energy Metabolism, pubmed-meshheading:20551287-Feeding Behavior, pubmed-meshheading:20551287-Hypothalamus, Middle, pubmed-meshheading:20551287-Immunohistochemistry, pubmed-meshheading:20551287-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:20551287-Male, pubmed-meshheading:20551287-Mice, pubmed-meshheading:20551287-Mice, Knockout, pubmed-meshheading:20551287-Motor Activity, pubmed-meshheading:20551287-Nerve Tissue Proteins, pubmed-meshheading:20551287-Neuropeptides, pubmed-meshheading:20551287-Oxygen Consumption, pubmed-meshheading:20551287-Rats, pubmed-meshheading:20551287-Rats, Wistar, pubmed-meshheading:20551287-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus.
pubmed:affiliation
Univ. of Miyazaki, Kiyotake, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't