Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin.

Abstract

BACKGROUND & AIMS Obesity is one of the risk factors for liver fibrosis, in which plasma adiponectin, an adipocytokine, levels are decreased. Hepatic stellate cells play central roles in liver fibrosis. When they are activated, they undergo transformation to myofibroblast-like cells. Adiponectin suppresses the proliferation and migration of vascular smooth muscle cells, whose characteristics are similar to those of hepatic stellate cells. Adiponectin could have biological significances in liver fibrosis. METHODS The role of adiponectin on liver fibrosis induced by the administration of carbon tetrachloride twice a week for 12 weeks was tested by using adiponectin-knockout mice and an adenovirus-mediated adiponectin-expression system. We also investigated the effect of adiponectin in activated hepatic stellate cells. RESULTS When mice were administered carbon tetrachloride (300 microL/kg body weight) twice a week for 12 weeks, knockout mice showed extensive liver fibrosis with an enhanced expression of transforming growth factor-beta 1 and connective tissue growth factor compared with wild-type mice (P < 0.05). Injection of adenovirus producing adiponectin (AdADN) before carbon tetrachloride (1000 microL/kg body weight) treatment prevented liver fibrosis in wild-type mice (P < 0.001). Injection of AdADN at 6 weeks attenuated liver fibrosis even though carbon tetrachloride was given for an additional 6 weeks (total of 12 weeks). In cultured hepatic stellate cells, adiponectin suppressed platelet-derived growth factor-induced proliferation and migration and attenuated the effect of transforming growth factor-beta 1 on the gene expression of transforming growth factor-beta 1 and connective tissue growth factor and on nuclear translocation of Smad2. CONCLUSIONS The findings indicate that adiponectin attenuates liver fibrosis and could be a novel approach in its prevention.

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@article{Kamada2003EnhancedCT, title={Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin.}, author={Yoshihiro Kamada and Shinji Tamura and Shinichi Kiso and Hitoshi Matsumoto and Yukiko Saji and Yuichi Yoshida and Koji Fukui and Norikazu Maeda and Hitoshi Nishizawa and Hiroyuki Nagaretani and Yoshihisa Okamoto and Shinji Kihara and Jun-ichiro Miyagawa and Yasuhisa Shinomura and Tohru Funahashi and Yuji Matsuzawa}, journal={Gastroenterology}, year={2003}, volume={125 6}, pages={1796-807} }