Document Detail


Plasma metabolomic profile in nonalcoholic fatty liver disease.
MedLine Citation:
PMID:  20423748     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The plasma profile of subjects with nonalcoholic fatty liver disease (NAFLD), steatosis, and steatohepatitis (NASH) was examined using an untargeted global metabolomic analysis to identify specific disease-related patterns and to identify potential noninvasive biomarkers. Plasma samples were obtained after an overnight fast from histologically confirmed nondiabetic subjects with hepatic steatosis (n = 11) or NASH (n = 24) and were compared with healthy, age- and sex-matched controls (n = 25). Subjects with NAFLD were obese, were insulin resistant, and had higher plasma concentrations of homocysteine and total cysteine and lower plasma concentrations of total glutathione. Metabolomic analysis showed markedly higher levels of glycocholate, taurocholate, and glycochenodeoxycholate in subjects with NAFLD. Plasma concentrations of long-chain fatty acids were lower and concentrations of free carnitine, butyrylcarnitine, and methylbutyrylcarnitine were higher in NASH. Several glutamyl dipeptides were higher whereas cysteine-glutathione levels were lower in NASH and steatosis. Other changes included higher branched-chain amino acids, phosphocholine, carbohydrates (glucose, mannose), lactate, pyruvate, and several unknown metabolites. Random forest analysis and recursive partitioning of the metabolomic data could separate healthy subjects from NAFLD with an error rate of approximately 8% and separate NASH from healthy controls with an error rate of 4%. Hepatic steatosis and steatohepatitis could not be separated using the metabolomic profile. Plasma metabolomic analysis revealed marked changes in bile salts and in biochemicals related to glutathione in subjects with NAFLD. Statistical analysis identified a panel of biomarkers that could effectively separate healthy controls from NAFLD and healthy controls from NASH. These biomarkers can potentially be used to follow response to therapeutic interventions.
Authors:
Satish C Kalhan; Lining Guo; John Edmison; Srinivasan Dasarathy; Arthur J McCullough; Richard W Hanson; Mike Milburn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-27
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  60     ISSN:  1532-8600     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-21     Completed Date:  2011-05-10     Revised Date:  2012-03-08    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  404-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA. sck@case.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Biological Markers / blood
Chromatography, High Pressure Liquid
Fatty Liver / blood
Female
Gas Chromatography-Mass Spectrometry
Humans
Male
Metabolome*
Metabolomics / methods*
Middle Aged
Tandem Mass Spectrometry
Grant Support
ID/Acronym/Agency:
1UL1 RR024989/RR/NCRR NIH HHS; DK079937/DK/NIDDK NIH HHS; R01 DK079937-01A1/DK/NIDDK NIH HHS; UL1 RR024989-02/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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