| CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. | |
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MedLine Citation:
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PMID: 12883487 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies suggest that hepatic cytochrome P450 2E1 (CYP2E1) activity is increased in individuals with chronic alcoholism, nonalcoholic steatohepatitis (NASH), and morbid obesity, and may contribute to liver disease. We studied 16 morbidly obese subjects with varying degrees of hepatic steatosis and 16 normal-weight controls. Obese subjects were evaluated at baseline, 6 weeks, and 1 year after gastroplasty, a procedure that leads to weight loss. Hepatic CYP2E1 activity was assessed by determination of the clearance of chlorzoxazone (CLZ), an in vivo CYP2E1-selective probe. Liver biopsy tissue was obtained during surgery for histopathology. Both the total and unbound oral CLZ clearance (Cl(u)/F) was elevated approximately threefold in morbidly obese subjects compared with controls (P <.001). The Cl(u)/F was significantly higher among subjects with steatosis involving >50% of hepatocytes, compared with those with steatosis in < or =50% of hepatocytes (P =.02). At postoperative week 6 and year 1, the median body mass index (BMI) of subjects who underwent gastroplasty decreased by 11% and 33%, total oral CLZ clearance declined by 16% (P <.01) and 46% (P <.05), and Cl(u)/F decreased by 18% (P <.05) and 35% (P =.16), respectively. Moreover, those subjects with a year 1 BMI <30 kg/m(2) exhibited a median Cl(u)/F that was 63% lower (P =.02) than the respective clearance for all other subjects. In conclusion, hepatic CYP2E1 activity is up-regulated in morbidly obese subjects. A positive association between the degree of steatosis and CYP2E1 activity preoperatively and between the extent of obesity and CYP2E1 activity postoperatively, suggests that CYP2E1 induction is related to or caused by hepatic pathology that results from morbid obesity. |
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Authors:
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Maurice G Emery; Jeannine M Fisher; Jenny Y Chien; Evan D Kharasch; E Patchen Dellinger; Kris V Kowdley; Kenneth E Thummel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 38 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-07-28 Completed Date: 2003-08-29 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 428-35 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blood Glucose Chlorzoxazone / diagnostic use, pharmacokinetics Cytochrome P-450 CYP2E1 / metabolism* Enzyme Activation Fatty Liver / metabolism*, pathology Female Gastric Bypass Humans Liver / enzymology*, pathology Male Muscle Relaxants, Central / diagnostic use, pharmacokinetics Obesity, Morbid / metabolism*, pathology, surgery Severity of Illness Index Weight Loss / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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ES02728/ES/NIEHS NIH HHS; GM48349/GM/NIGMS NIH HHS; GM48712/GM/NIGMS NIH HHS; K24 DK02957/DK/NIDDK NIH HHS; M01 RR00037/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Muscle Relaxants, Central; 95-25-0/Chlorzoxazone; EC 1.14.14.1/Cytochrome P-450 CYP2E1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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