Leptin administration exacerbates thioacetamide-induced liver fibrosis in mice

AIM: To investigate the effects of leptin administration on liver fibrosis induced by thioacetamide (TAA). METHODS: Twenty-four male C57Bl/6 mice were randomly allocated into four groups, which were intra-peritoneally given saline (2 mL/kg), leptin (1 mg/kg), TAA (200 mg/kg), TAA (200 mg/kg) plus leptin (1 mg/kg) respectively, thrice a week. All mice were killed after 4 wk. The changes in biochemical markers, such as the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver were determined. For histological analysis, liver tissues were fixed with 10% buffered formalin, embedded with paraffin. Hematoxylin-eosin (HE) staining and picric acid-Sirius red dyeing were performed. The level of alpha 1(I) procollagen mRNA in liver tissues was analyzed by RT- PCR. RESULTS: Apparent liver fibrosis was found in TAA group and TAA plus leptin group. Compared to saline group, the levels of ALT and AST in serum and MDA in liver increased in TAA group (205.67 +/- 27.69 U/L vs 50.67 +/- 10.46 U/L, 177.50 +/- 23.65U/L vs 76.33 +/- 12.27 U/L, 2.60 +/- 0.18 nmol/mg pro vs 1.91 +/- 0.14 nmol/ mg pro, P<0.01) and in TAA plus leptin group (256.17 +/- 22.50 U/L vs 50.67 +/- 10.46 U/L, 234.17 +/- 27.37 U/L vs 76.33 +/- 12.27 U/L, 2.97 +/- 0.19 nmol/mg pro vs 1.91 +/- 0.14 nmol/mg pro, P<0.01). The level of SOD in livers decreased (51.80 +/- 8.36 U/mg pro vs 81.52 +/- 11.40 U/mg pro, 35.78 +/- 6.11 U/mg pro vs 81.52 +/- 11.40 U/mg pro, P<0.01) and the level of alpha 1(I) procollagen mRNA in liver tissues also increased (0.28 +/- 0.04 vs 0.11 +/- 0.02, 0.54 +/- 0.07 vs 0.11 +/- 0.02, P<0.01). But no significant changes were found in leptin group and saline group. Compared to TAA group, ALT, AST, MDA, and alpha 1(I) procollagen mRNA and grade of liver fibrosis in TAA plus leptin group increased (256.17 +/- 22.50 U/L vs 205.67 +/- 27.69 U/L, P<0.05; 234.17 +/- 27.37 U/L vs 177.50 +/- 23.65 U/L, P< 0.05; 2.97 +/- 0.19 nmol/mg pro vs 2.60 +/- 0.18 nmol/mg pro, P<0.05; 0.54 +/- 0.07 vs 0.28 +/- 0.04, P<0.01; 3.17 vs 2.00, P<0.05), and the level of SOD in liver decreased (35.78 +/- 6.11 U/mg pro vs 51.80 +/- 8.36 U/mg pro, P<0.05). There were similar changes in the degree of type I collagen deposition confirmed by picric acid-Sirius red dyeing. CONCLUSION: Leptin can exacerbate the degree of TAA-induced liver fibrosis in mice. Leptin may be an important factor in the development of liver fibrosis. (c) 2005 The WJG Press and Elsevier Inc. All rights reserved.