RGD Reference Report - Competitive inhibition of leptin signaling results in amelioration of liver fibrosis through modulation of stellate cell function. - Rat Genome Database

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Competitive inhibition of leptin signaling results in amelioration of liver fibrosis through modulation of stellate cell function.

Authors: Elinav, E  Ali, M  Bruck, R  Brazowski, E  Phillips, A  Shapira, Y  Katz, M  Solomon, G  Halpern, Z  Gertler, A 
Citation: Elinav E, etal., Hepatology. 2009 Jan;49(1):278-86.
RGD ID: 5128713
Pubmed: PMID:19065677   (View Abstract at PubMed)
DOI: DOI:10.1002/hep.22584   (Journal Full-text)

Leptin signaling is involved in T-cell polarization and is required for profibrotic function of hepatic stellate cells (HSCs). Leptin-deficient ob/ob mice do not develop liver fibrosis despite the presence of severe long-standing steatohepatitis. Here, we blocked leptin signaling with our recently generated mouse leptin antagonist (MLA), and examined the effects on chronic liver fibrosis in vivo using the chronic thioacetamide (TAA) fibrosis model, and in vitro using freshly-isolated primary HSCs. In the chronic TAA fibrosis model, leptin administration was associated with significantly enhanced liver disease and a 100% 5-week to 8-week mortality rate, while administration or coadministration of MLA markedly improved survival, attenuated liver fibrosis, and reduced interferon gamma (IFN-gamma) levels. No significant changes in weight, serum cholesterol, or triglycerides were noted. In vitro administration of rat leptin antagonist (RLA), either alone or with leptin, to rat primary HSCs reduced leptin-stimulated effects such as increased expression of alpha-smooth muscle actin (alpha-SMA), and activation of alpha1 procollagen promoter. Conclusion: Inhibition of leptin-enhanced hepatic fibrosis may hold promise as a future antifibrotic therapeutic modality.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Cirrhosis disease_progressionISOLep (Mus musculus)5128713; 5128713 RGD 
Experimental Liver Cirrhosis disease_progressionIMP 5128713 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lep  (leptin)

Genes (Mus musculus)
Lep  (leptin)

Genes (Homo sapiens)
LEP  (leptin)


Additional Information