Both Rosiglitazone and Oleate Protect MCD-Induced Hepatotoxicity but via Different Ways

Lee, Ji Young; Park, Se Eun; Park, Eun Mi; Jung, Tae Woo; Lee, Jae Hyuk; Kang, Eun Seok; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo
June 2007
Diabetes;Jun2007 Supplement 1, Vol. 56, pA451
Academic Journal
Background: Failure of fatty acid oxidation and pro-inflammatory cytokine mediated hepatocyte injury has been implicated as a cause of nonalcoholic steatohepatitis (NASH). We compared the efficacy of rosiglitazone versus oleate against methionine choline deficient diet (MCD)-induced NASH mice model. Methods: Rosiglitazone (20 mg/Kg) or oleate (0.5 mg/g) were given orally once daily to 8 weeks old male C57BL/6J mice fed with a MCD diet for 4 weeks. The mice were divided into 4 groups (n=10/group): normal diet (N), MCD diet (M), rosiglitazone with MCD diet (R) and oleate with MCD diet (O). In this study, we examined morphometric analysis, plasma alanine aminotransferase (ALT) and the level of liver mRNA expression for acyl-CoA oxidase (ACO), monocyte chemoattractant protein 1 (MCP1), tumor-necrosis factor-α (TNFα), and matrix metalopeptidase 9 (MMP9) by RT-PCR. Results: Fat droplets was almost completely absent in group O. Interestingly, in group R, fat droplets area does not changed as compared with group M but have no presence of cell swelling. Plasma ALT levels were significantly lower both group R and group O as compared with group M (by 29% and 32%, p<0.05). The expression of ACO in livers was significantly increased in group O as compared with group M (by 12.8%, p<0.05) while there is no difference between group R and group M. The expression of MCP1, TNF-α and MMP9 in livers was significantly decreased in both group R (by 35.2%, 38.5% and 24.0% p<0.05 for all) and group O (22.2%, 37.3% and 24.2% p<0.05 for all) as compared with group M. Conclusion: These observations show that rosiglitazone and oleate play important roles in the prevention of NASH but via different mechanism. Oleate provided significant improvement in both hepatic clearance of fatty acids and pro-inflammatory cytokine-mediated hepatocyte injury. Rosiglitazone did not influence fat accumulation but protected fat-derived inflammatory response. These suggest that both rosiglitazone and oleate may be useful therapeutic agents for treatment of NASH in different aspects.


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