NDLI: Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lu, Yongke Zhuge, Jian Wang, Xiaodong Bai, Jingxiang Cederbaum, Arthur I.
Description	Country affiliation: United States Author Affiliation: Lu Y ( Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.)
Abstract	Cytochrome P450 2E1 (CYP2E1) is suggested to play a role in alcoholic liver disease, which includes alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. In this study, we investigated whether CYP2E1 plays a role in experimental alcoholic fatty liver in an oral ethanol-feeding model. After 4 weeks of ethanol feeding, macrovesicular fat accumulation and accumulation of triglyceride in liver were observed in wild-type mice but not in CYP2E1-knockout mice. In contrast, free fatty acids (FFAs) were increased in CYP2E1-knockout mice but not in wild-type mice. CYP2E1 was induced by ethanol in wild-type mice, and oxidative stress induced by ethanol was higher in wild-type mice than in CYP2E1-knockout mice. Peroxisome proliferator-activated receptor alpha (PPARalpha), a regulator of fatty acid oxidation, was up-regulated in CYP2E1-knockout mice fed ethanol but not in wild-type mice. A PPARalpha target gene, acyl CoA oxidase, was decreased by ethanol in wild-type but not in CYP2E1-knockout mice. Chlormethiazole, an inhibitor of CYP2E1, lowered macrovesicular fat accumulation, inhibited oxidative stress, and up-regulated PPARalpha protein level in wild-type mice fed ethanol. The introduction of CYP2E1 to CYP2E1-knockout mice via an adenovirus restored macrovesicular fat accumulation. These results indicate that CYP2E1 contributes to experimental alcoholic fatty liver in this model and suggest that CYP2E1-derived oxidative stress may inhibit oxidation of fatty acids by preventing up-regulation of PPARalpha by ethanol, resulting in fatty liver.
File Format	HTM / HTML
ISSN	02709139
Issue Number	5
Volume Number	47
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2008-05-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Cytochrome P-450 Cyp2e1 Metabolism Ethanol Toxicity Fatty Liver, Alcoholic Enzymology Alanine Transaminase Blood Animals Deficiency Genetics Disease Models, Animal Fatty Acids, Nonesterified Pathology Female Immunohistochemistry Liver Mice Mice, Knockout Ppar Alpha Thiobarbituric Acid Reactive Substances Triglycerides Tumor Necrosis Factor-alpha Journal Article Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Hepatology

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