Document Detail


Phosphatidylethanolamine-N-methyltransferase activity and dietary choline regulate liver-plasma lipid flux and essential fatty acid metabolism in mice.
MedLine Citation:
PMID:  14608048     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphatidylethanolamine-N-methyltransferase (PEMT) catalyzes the methylation of phosphatidylethanolamine to form phosphatidylcholine (PC) and represents one of the two major pathways for PC biosynthesis. Mice with a homozygous disruption of the PEMT gene are dependent on the 1,2-diacylglycerol cholinephosphotransferase (CDP-choline) pathway for the synthesis of PC and develop severe liver steatosis when fed a diet deficient in choline. The present study used quantitative lipid metabolite profiling to characterize lipid metabolism in PEMT-deficient mice fed diets containing varying concentrations of choline. Choline supplementation restored liver, but not plasma PC concentrations of PEMT-deficient mice to levels commensurate with control mice. Choline supplementation also restored plasma triglyceride concentrations to normal levels, but did not restore plasma cholesterol ester concentrations in the PEMT-deficient mice to those equal to control mice. PEMT-deficient mice also had substantially diminished concentrations of docosahexaenoic acid [22:6(n-3)] and arachidonic acid [20:4(n-6)] in plasma, independent of choline status. Thus, choline supplementation rescued some but not all of the phenotypes induced by the knockout. These findings indicate that PEMT activity functions beyond its recognized role as a compensatory pathway for PC biosynthesis and that, in contrast, PEMT activity is involved in many physiologic processes including the flux of lipid between liver and plasma and the delivery of essential fatty acids to blood and peripheral tissues via the liver-derived lipoproteins.
Authors:
Steven M Watkins; Xiaonan Zhu; Steven H Zeisel
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of nutrition     Volume:  133     ISSN:  0022-3166     ISO Abbreviation:  J. Nutr.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-10     Completed Date:  2004-08-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3386-91     Citation Subset:  IM    
Affiliation:
Lipomics Technologies, Incorporated, West Sacramento, CA 95691, USA. steve.watkins@lipomics.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Cholesterol Esters / metabolism
Choline / administration & dosage,  pharmacology*
Diet
Fatty Acids, Essential / metabolism*
Lipid Metabolism*
Lipids / blood
Liver / drug effects,  metabolism*
Methyltransferases / deficiency*,  genetics,  metabolism*
Mice
Mice, Knockout
Phosphatidylethanolamine N-Methyltransferase
Phospholipids / metabolism
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
AG09525/AG/NIA NIH HHS; DK55865/DK/NIDDK NIH HHS; DK56350/DK/NIDDK NIH HHS; ES10126/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Cholesterol Esters; 0/Fatty Acids, Essential; 0/Lipids; 0/Phospholipids; 0/Triglycerides; 62-49-7/Choline; EC 2.1.1.-/Methyltransferases; EC 2.1.1.17/Phosphatidylethanolamine N-Methyltransferase

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


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