Leptin enhances the effect of transforming growth factor beta in increasing type I collagen formation

Hepatic fibrosis produced by carbon tetrachloride and by Schistosoma masoni is markedly decreased in leptin deficient ob/ob mice as compared to control mice. Leptin is present in activated rat stellate cells, which are the principal collagen producing cells in the liver. The purpose of this study was to identify the leptin receptor and to determine the effects of leptin on type I collagen expression in the human stellate cell line, LX-1. Leptin protein was detected in the LX-1 cells. The leptin receptor (OB-R) was demonstrated by immunofluorescent staining and confocal microscopy. However, only the short forms (Ob-R(s)), but not the long forms (Ob-R(l)), of leptin receptor mRNA expression were detected. Leptin increased alpha(1)(I) collagen mRNA and type I collagen production. Leptin did not increase TGFbeta1 mRNA or protein in the cultured LX-1 cells. Leptin, however, increased TGFbeta type II receptor mRNA and protein and augmented the effect of TGFbeta1 on collagen production. In conclusion, this study shows that the effect of leptin in increasing type I collagen production in stellate cells is mediated by actions of leptin in increasing the effectiveness of TGFbeta on fibrogenesis by means of an enhancement of the TGFbeta type II receptor.