Leptin deficiency reduces but does not eliminate the development of hepatic fibrosis in mice infected with Schistosoma mansoni.
OBJECTIVE
Leptin, a product of the obese (ob) gene, was demonstrated previously in activated hepatic collagen-producing stellate cells, but not in quiescent retinol-storing stellate cells. The role of leptin in fibrogenesis is unknown. This study investigated the possible influence of leptin in the pathogenesis of fibrosis by determination of the amount of fibrosis produced by Schistosoma mansoni infection in leptin deficient male ob/ob mice as compared to control mice.


METHODS
The mice were infected percutaneously with cercaria of Schistosoma mansoni and the amount of liver fibrosis determined 12 weeks after infection. The amount of hepatic collagen deposited was quantified by morphometric analysis of liver sections stained with sirius red and by hydroxyproline content.


RESULTS
The amount of histologically detectable fibrosis was greater in the infected controls than in the infected ob/ob mice. In the infected control mice, but not in the ob/ob mice, the fibrosis surrounding the granuloma was broad and extended beyond the portal tracts into the lobule with the formation of fibrous septa.


CONCLUSIONS
This study shows that leptin is a potentiating, but not an essential factor, for the development of hepatic fibrosis, because leptin deficiency reduces but does not prevent the development of hepatic fibrosis.
Potter
James J
JJ
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA.
Mezey
Esteban
E
D000818:Animals; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D006099:Granuloma / Q000469:parasitology / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D020738:Leptin / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese / Q000235:genetics / Q000502:physiology; D012550:Schistosoma mansoni / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D020738:Leptin; D003094:Collagen; D006909:Hydroxyproline