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Leptin is required for fibrogenic responses induced by thioacetamide in the murine liver
Author(s) -
Honda Hajime,
Ikejima Kenichi,
Hirose Miyoko,
Yoshikawa Mutsuko,
Lang Tie,
Enomoto Nobuyuki,
Kitamura Tsuneo,
Takei Yoshiyuki,
Sato Nobuhiro
Publication year - 2002
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2002.33684
Subject(s) - thioacetamide , leptin , endocrinology , medicine , hepatic fibrosis , procollagen peptidase , fibrosis , chemistry , biology , obesity
In this study, we investigated hepatic fibrogenesis caused by long‐term thioacetamide (TAA) administration in ob/ob mice, a naturally occurring leptin deficient animal. In the lean littermates, prominent hepatic fibrosis, as well as positive staining for α smooth muscle actin (α‐SMA), was induced by treatment with TAA (200 μg/g, IP, 3 times per week) for 4 to 8 weeks as expected. In sharp contrast, almost no hepatic fibrosis developed in ob/ob mice given the equivalent doses of TAA, where specific staining for α‐SMA barely was detected. Induction of α1(I) procollagen mRNA caused by TAA also was prevented in ob/ob mice almost completely. Further, transforming growth factor β (TGF‐β) mRNA was increased in the liver after TAA treatment for 4 weeks in lean littermates, which also was prevented in ob/ob mice. Interestingly, fibrotic septa in the hepatic lobules, as well as increases in α1(I) procollagen mRNA, was observed in ob/ob mice, when they were injected with recombinant murine leptin (1 μg/g daily) in combination with TAA treatment. Leptin per se did not cause any fibrotic changes in the liver in ob/ob mice. These findings clearly indicated that leptin deficiency is responsible for the resistance to TAA‐induced profibrogenic responses in ob/ob mice. In conclusion, leptin appears to promote profibrogenic responses in the liver, in part, by up‐regulation of TGF‐β.