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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34219

Cordani, C. Involvement of nitric oxide in disease-related anorexia. 2010, University of Zurich, Vetsuisse Faculty.

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Abstract

The nitric oxide (NO) producing enzyme inducible NO synthase isoform (iNOS) is strongly upregulated under inflammatory conditions in the arcuate nucleus, a hypothalamic key structure for the control of food intake and energy balance. This project aims to prove the concept that a pharmacological blockade of iNOS attenuates anorexia and associated disease symptoms induced by the proinflammatory endotoxin lipopolysaccharide (LPS). We also analyzed the association between LPS-induced anorexia and pSTAT3-formation in the arcuate nucleus and in hindbrain feeding centers (AP/NTS region). pSTAT3 is a cytokine dependent transcription factor, which is suggested to control iNOS expression. Findings and conclusions: NO contributes to LPS-induced anorexia because anorexia is attenuated by the specific iNOS-inhibitor 1400W. In addition, 1400W treatment also ameliorates other LPS-induced symptoms (e.g. adipsia, fever, inactivity). LPS treatment induces a time-dependent pSTAT3 formation in the ARC and the AP/NTS region of rats; this parallels the time course of LPS anorexia. LPS does not induce a pSTAT3 response in LPS tolerant rats that do not show an anorectic LPS response either. These findings provide evidence that NO is involved in disease-related anorexia and that pharmacological iNOS blockade may be a therapeutic approach to treat sickness anorexia/cachexia. LPS anorexia is associated with enhanced pSTAT3 signaling. Which might be involved in the underlying transcriptional mechanisms.

Item Type:Dissertation
Referees:Riediger T, Schmid H
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
DDC:570 Life sciences; biology
Language:English
Date:2010
Deposited On:08 Jun 2010 19:51
Last Modified:18 Oct 2012 00:09
Number of Pages:51
Related URLs:https://biblio.unizh.ch/F/?local_base=UZH01&con_lng=GER&func=find-b&find_code=SYS&request=001908633

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