Constitutive androstane receptor agonist, TCPOBOP, attenuates steatohepatitis in the methionine choline-deficient diet-fed mouse.
World J Gastroenterol
; 13(42): 5635-41, 2007 Nov 14.
Article
em En
| MEDLINE
| ID: mdl-17948939
ABSTRACT
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 omega-oxidation and peroxisomal beta-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.
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Fatores de Transcrição
/
Deficiência de Colina
/
Receptores Citoplasmáticos e Nucleares
/
Fígado Gorduroso
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article