Influence of leptin in the development of hepatic fibrosis produced in mice by Schistosoma mansoni infection and by chronic carbon tetrachloride administration.
OBJECTIVE
Leptin, a product of the obese (ob) gene is present in activated stellate cells. This study investigated whether leptin is essential for the development of hepatic fibrosis caused by various agents.


METHODS
Control and ob/ob mice were infected with Schistosoma mansoni or were administered chronic carbon tetrachloride to cause hepatic fibrosis.


RESULTS
Fibrosis developed in both ob/ob and control mice. However, the amount of histologically detectable fibrosis and the increase in liver hydroxyproline content was significantly greater in both models of fibrosis for treated controls than for treated ob/ob mice. Fibrosis was associated with higher secretion of TGFbeta1 from spleen cells of treated control than treated ob/ob mice. Chronic leptin administration in ob/ob mice infected with Schistosoma mansoni resulted in an increase in the amount of fibrosis caused by Schistosoma mansoni, eliminating any significant differences in the amount of fibrosis between infected ob/ob mice and control mice. It also eliminated any significant difference in TGFbeta1 secretion between the infected ob/ob and infected control mice.


CONCLUSIONS
This study shows that leptin deficiency decreases but does not eliminate hepatic fibrosis produced by Schistosoma mansoni and carbon tetrachloride administration. The effect of leptin in potentiating fibrogenesis is most likely mediated by TGFbeta1.
Potter
James J
JJ
Department of Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205-2195, USA.
Rennie-Tankesley
Lynda
L
Mezey
Esteban
E
D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D020738:Leptin / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000150:complications / Q000469:parasitology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000150:complications*; D013154:Spleen / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D020738:Leptin; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride