| 1 | Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse显示文摘AIM:To ascertain whether constitutive androstane receptor(CAR)activation by 1,4-bis-2-(3,5,-dichloropyridyloxy)benzene(TCPOBOP)modulates steatohepatitis in the methionine choline-deficient(MCD)diet-fed animal.METHODS:C57/BL6 wild-type mice were fed the MCD or standard diet for 2 wk and were treated with either the CAR agonist,TCPOBOP,or the CAR inverse agonist,androstanol.RESULTS:Expression of CYP2B10 and CYP3A11,known CAR target genes,increased 30-fold and 45-fold,respectively,in TCPOBOP-treated mice fed the MCD diet.TCPOBOP treatment reduced hepatic steatosis(44.6 ± 5.4% vs 30.4 ± 4.5%,P < 0.05)and serum triglyceride levels(48 ± 8 vs 20 ± 1 mg/dL,P < 0.05)in MCD diet-fed mice as compared with the standard diet-fed mice.This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal ω-oxidation and peroxisomal β-oxidation,namely CYP4A10,LPBE,and 3-ketoacyl-CoA thiolase.The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation.In contrast,androstanol was without effect on any of the above parameters.CONCLUSION:CAR activation stimulates induction of genes involved in fatty acid oxidation,and ameliorates hepatic steatosis,apoptosis and inflammation. | Edwina S Baskin-Bey Akira Anan Hajime Isomoto Steven F Bronk Gregory J Gores | 2007 | World Journal of Gastroenterology2007，13，42： | 3 |
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