RGD Reference Report - Modulation of circulating leptin levels by its soluble receptor. - Rat Genome Database

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Modulation of circulating leptin levels by its soluble receptor.

Authors: Huang, L  Wang, Z  Li, C 
Citation: Huang L, etal., J Biol Chem 2001 Mar 2;276(9):6343-9.
RGD ID: 61790
Web Url: http://www.jbc.org/cgi/content/full/276/9/6343
Pubmed: PMID:11102451   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M009795200   (Journal Full-text)

Leptin is an adipocyte-derived hormone with potent weight reducing effects. Genetically obese rodents with mutations of leptin or the leptin receptor are defective in leptin signaling and develop morbid obesity and diabetes. Interestingly, the levels of both leptin mRNA and protein are increased by up to 20-fold in these animals, suggesting the existence of a feedback mechanism controlling the amount of leptin in circulation. In this report, we attempted to determine whether the up-regulation of circulating leptin in Zucker Diabetic Fatty rats, which are nonresponsive to leptin due to a receptor point mutation, is entirely due to increased expression of leptin. We demonstrate that the high level of circulating leptin in these rats is attributable to at least two factors: increased leptin expression by the adipose tissue and delayed clearance of leptin from circulation due to binding to its soluble receptor. The latter conclusion was supported by three lines of evidence: 1) The soluble leptin receptor is up-regulated by about 20-fold in Zucker Diabetic Fatty rats; 2) Adenovirus-mediated overexpression of the soluble leptin receptor results in a similar -fold increase of circulating leptin; 3) In ob/ob mice, which have no endogenous leptin, exogenously administered leptin reaches a higher level when the soluble leptin receptor is overexpressed. The weight-reducing effect of leptin is enhanced in C57Bl/6 ob/ob mice with overexpression of the soluble leptin receptor. Soluble leptin receptor may be a significant factor determining the amount of total leptin in circulation.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LepRataltered energy homeostasis pathway  TAS  RGD 
LeprRataltered energy homeostasis pathway  TAS  RGD 
LepRataltered leptin system pathway  TAS  RGD 
LeprRataltered leptin system pathway  TAS  RGD 
LeprRatenergy homeostasis pathway  TAS  RGD 
LepRatleptin system pathway   TAS  RGD 
LeprRatleptin system pathway   TAS  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Lep  (leptin)
Lepr  (leptin receptor)


Additional Information