Document Detail


In vivo and in vitro evidence for a hepatic modulation of the leptin signal in rats.
MedLine Citation:
PMID:  15606726     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Leptin is primarily secreted by the adipose tissue. It binds not only to hypothalamic structures involved in energy regulation but also to many peripheral tissues including the liver. Leptin circulates in free and receptor-bound forms. Both components are differentially regulated under various pathophysiological conditions and serve different physiological functions. They are released from adipose tissue but previous data suggest an additional formation outside the fat compartment. Here we tested the contribution of the liver in binding and modulating leptin in the circulation. MATERIALS AND METHODS: In vivo experiments were performed with radioactive labelled leptin with and without pretreatment with unlabelled leptin in freely moving, chronic intravenously cannulated male rats. Livers were investigated by immunohistochemistry and in situ hybridization and immunoblotting was performed, followed by ex vivo liver perfusion studies with human recombinant leptin. RESULTS: In in vivo experiments radioactively labelled leptin (at low concentrations) is avidly bound to rat liver (greater than 80% of basal serum values 90 min following i.v. infusion). Pre-treatment with excess of unlabelled leptin in vivo revealed a rapid hepatic down-regulation of leptin receptor isoforms when tested by in situ hybridization, immunoblotting or immunohistochemistry. Ex vivo perfusion of rat liver with human recombinant leptin induced a dose- and time-dependent formation of receptor-bound leptin in the perfusate. CONCLUSIONS: The present data support an active role of the liver in the modulation of the leptin signal through different regulation of the soluble leptin receptor, the bound and free forms of the hormone, which may have important implications for leptin's central efficacy and the development of 'leptin resistance'.
Authors:
G Brabant; H Nave; R Horn; C Anderwald; G Müller; M Roden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of clinical investigation     Volume:  34     ISSN:  0014-2972     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-20     Completed Date:  2005-03-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  England    
Other Details:
Languages:  eng     Pagination:  831-7     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. brabant.georg@mh-hannover.de
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / metabolism
Animals
Leptin / pharmacokinetics*
Liver / metabolism*
Male
Rats
Rats, Inbred Lew
Receptors, Cell Surface / metabolism
Receptors, Leptin
Recombinant Proteins / pharmacokinetics
Signal Transduction / physiology
Tissue Distribution
Chemical
Reg. No./Substance:
0/Leptin; 0/Receptors, Cell Surface; 0/Receptors, Leptin; 0/Recombinant Proteins; 0/leptin receptor, human

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