Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-10-11
pubmed:abstractText
Treatment with the bacterial endotoxin lipopolysaccharide (LPS) is a commonly used model to induce disease-related anorexia. Following LPS treatment inducible nitric oxide synthase (iNOS) is expressed in the hypothalamic arcuate nucleus (ARC), where nitric oxide (NO) inhibits orexigenic neurons. Intracellular STAT signaling is triggered by inflammatory stimuli and has been linked to the transcriptional regulation of iNOS. We evaluated whether pharmacological blockade of iNOS by the specific inhibitor 1400W attenuates LPS-induced anorexia. Furthermore, we hypothesized that the tolerance to the anorectic effect occurring after repeated LPS treatment is paralleled by a blunted STAT3 phosphorylation in the ARC. Rats treated with a subcutaneous injection of 1400W (10 mg/kg) showed an attenuated anorectic LPS response relative to control rats receiving only LPS (100 µg/kg; i.p.). Similarly, iNOS blockade attenuated LPS-induced adipsia, hyperthermia, inactivity and the concomitant drop in energy expenditure. While single LPS treatment increased STAT3 phosphorylation in the ARC, rats treated repeatedly with LPS showed no anorectic response and also no STAT3 phosphorylation in the ARC after the second and third LPS injections, respectively. Hence, pSTAT3 signaling in the ARC might be part of the intracellular cascades translating pro-inflammatory stimuli into suppression of food intake. The current findings substantiate a role of iNOS dependent NO formation in disease-related anorexia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1873-5177
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
112-20
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Involvement of nitric oxide in lipopolysaccharide induced anorexia.
pubmed:affiliation
Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland. triedig@vetphys.uzh.ch
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't