Constitutive and Inducible Expression of Hepatic CYP2E1 in Leptin-deficient ob/ob Mice

doi:10.1006/bbrc.2000.2125

Biochemical and Biophysical Research Communications

Volume 268, Issue 2, 16 February 2000, Pages 337-344

https://doi.org/10.1006/bbrc.2000.2125 Get rights and content

Abstract

In this study we have analyzed the inducible as well as constitutive hepatic expression of Cyp2e1 in a genetic model of obesity and non-insulin dependent (type II) diabetes, the leptin-deficient ob/ob mouse. In obese mice, Cyp2e1 levels were decreased compared to lean littermates. Treatment with leptin increased hepatic Cyp2e1 in obese mice to the levels observed in lean animals, but failed to alter Cyp2e1 expression in lean animals. As expected, leptin also reduced food intake in treated mice compared to saline-treated controls. In obese mice pair-fed the reduced amount of food, there was a significant increase in Cyp2e1 mRNA but no increase in Cyp2e1 protein or enzyme activity. Fasting and administration of acetone and 4-methylpyrazole increased Cyp2e1 mRNA as well as protein and activity in both obese and lean mice. The present data indicate that while Cyp2e1 is still inducible in obese mice by xenobiotics and fasting, full constitutive expression of Cyp2e1 requires leptin to be present. This effect of leptin appears to be at least partly independent of the hypothalamic control of food intake.

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^☆: Abbreviations used: CYP2E1, Cytochrome P450 2E1; NASH, nonalcoholic steatohepatitis

¹: To whom correspondence should be addressed. Fax: +61-02-9635 7582. E-mail: [email protected].

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Regular ArticleConstitutive and Inducible Expression of Hepatic CYP2E1 in Leptin-deficient ob/ob Mice☆

Abstract

J. Biol. Chem.

J. Biol. Chem.

Toxicol. App. Pharmacol.

Exp. Mol. Pathol.

Gastroenterology

J. Hepatol.

Gastroenterology

J. Nutr.

Biochem. Biophys. Res. Commun.

Arch. Biochem. Biophys.

Chem. Biol. Interact.

Biochem. Biophys. Res. Commun.

J. Hepatol.

Biochem. Pharmacol.

Eur. J. Pharmacol.

Arch. Biochem. Biophys.

J. Biol. Chem.

Arch. Biochem. Biophys.

Biochem. Pharmacol.

Arch. Biochem. Biophys.

J. Pharmacol. Exp. Ther.

Hepatology

Mol. Endocrinol.

Regular Article
Constitutive and Inducible Expression of Hepatic CYP2E1 in Leptin-deficient ob/ob Mice☆