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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-11-11
pubmed:abstractText
Leptin regulates feeding behavior and energy metabolism by affecting hypothalamic neuromodulators. The present study was designed to examine hypothalamic neuronal histamine, a recently identified mediator of leptin signaling in the brain, in genetic obese animals. Concentrations of hypothalamic histamine and tele-methylhistamine (t-MH), a major histamine metabolite, were significantly lower in obese (ob/ob) and diabetic (db/db) mice, and Zucker fatty (fa/fa) rats, leptin-deficient and leptin-receptor defective animals, respectively, relative to lean littermates (P < 0.05 for each). A bolus infusion of leptin (1.0 microg) into the lateral ventricle (ilvt) significantly elevated the turnover rate of hypothalamic neuronal histamine, as assessed by pargyline-induced accumulation of t-MH, in ob/ob mice compared with phosphate-buffered saline (PBS) infusions (P < 0.05). However, this same treatment did not affect hypothalamic histamine turnover in db/db mice. In agouti yellow (A(y)/a) mice, animals defective in pro-opiomelanocortin (POMC) signaling, normal levels of histamine, and t-MH were seen in the hypothalamus at 4 weeks of age when obesity had not yet developed. These amine levels in A(y)/a mice showed no change until 16 weeks of age, although the mice were remarkably obese by this time. Infusions of corticotropin releasing hormone (CRH), one of neuropeptide related to leptin signaling, into the third ventricle (i3vt) increased histamine turnover in the hypothalamus of Wistar King A rats (P < 0.05 versus PBS infusion). Infusion of neuropeptide Y (NPY) or alpha-melanocyte stimulating hormone (MSH), a POMC-derived peptide failed to increase histamine turnover. These results indicate that lowered activity of hypothalamic neuronal histamine in ob/ob and db/db mice, and fa/fa rats may be due to insufficiency of leptin action in the brains of these animals. These results also suggest that disruption of POMC signaling in A(y)/a mice may not impact on neuronal histamine. Moreover, CRH but neither POMC-derived peptide nor NPY may act as a signal to neuronal histamine downstream of the leptin signaling pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1535-3702
pubmed:author
pubmed:issnType
Print
pubmed:volume
228
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1132-7
pubmed:meshHeading
pubmed-meshheading:14610251-Animals, pubmed-meshheading:14610251-Corticotropin-Releasing Hormone, pubmed-meshheading:14610251-Disease Models, Animal, pubmed-meshheading:14610251-Histamine, pubmed-meshheading:14610251-Hypothalamus, pubmed-meshheading:14610251-Injections, Intraventricular, pubmed-meshheading:14610251-Leptin, pubmed-meshheading:14610251-Male, pubmed-meshheading:14610251-Methylhistamines, pubmed-meshheading:14610251-Mice, pubmed-meshheading:14610251-Mice, Inbred C57BL, pubmed-meshheading:14610251-Mice, Obese, pubmed-meshheading:14610251-Neuropeptide Y, pubmed-meshheading:14610251-Obesity, pubmed-meshheading:14610251-Pro-Opiomelanocortin, pubmed-meshheading:14610251-Rats, pubmed-meshheading:14610251-Rats, Wistar, pubmed-meshheading:14610251-Rats, Zucker, pubmed-meshheading:14610251-Third Ventricle, pubmed-meshheading:14610251-alpha-MSH
pubmed:year
2003
pubmed:articleTitle
Hypothalamic neuronal histamine in genetically obese animals: its implication of leptin action in the brain.
pubmed:affiliation
Department of Internal Medicine I, School of Medicine, Oita Medical University, Hasama, Oita 879-5593, Japan.
pubmed:publicationType
Journal Article