Document Detail


Elimination of the CDP-ethanolamine pathway disrupts hepatic lipid homeostasis.
MedLine Citation:
PMID:  19666474     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphoethanolamine cytidylyltransferase (ECT) catalyzes the rate-controlling step in a major pathway for the synthesis of phosphatidylethanolamine (PtdEtn). Hepatocyte-specific deletion of the ECT gene in mice resulted in normal appearing animals without overt signs of liver injury or inflammation. The molecular species of PtdEtn in the ECT-deficient livers were significantly altered compared with controls and matched the composition of the phosphatidylserine (PtdSer) pool, illustrating the complete reliance on the PtdSer decarboxylase pathway for PtdEtn synthesis. PtdSer structure was controlled by the substrate specificity of PtdSer synthase that selectively converted phosphatidylcholine molecular species containing stearate paired with a polyunsaturated fatty acid to PtdSer. There was no evidence for fatty acid remodeling of PtdEtn. The elimination of diacylglycerol utilization by the CDP-ethanolamine pathway led to a 10-fold increase in triacylglycerols in the ECT-deficient hepatocytes that became engorged with lipid droplets. Triacylglycerol accumulation was associated with a significant elevation in the expression of the transcription factors and target genes that drive de novo lipogenesis. The absence of the ECT pathway for diacylglycerol utilization at the endoplasmic reticulum triggers increased fatty acid synthesis to support the formation of triacylglycerols leading to liver steatosis.
Authors:
Roberta Leonardi; Matthew W Frank; Pamela D Jackson; Charles O Rock; Suzanne Jackowski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-08-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-05     Completed Date:  2009-10-21     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27077-89     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytidine Diphosphate / metabolism*
Ethanolamine / metabolism*
Fatty Liver / genetics,  metabolism
Female
Gene Expression Regulation
Gene Knockout Techniques
Homeostasis* / genetics
Lipid Metabolism* / genetics
Lipogenesis / genetics
Liver / metabolism*
Male
Mice
Organ Specificity
Phosphatidylethanolamines / biosynthesis
RNA Nucleotidyltransferases / deficiency,  genetics,  metabolism*
RNA, Messenger / metabolism
Transcription, Genetic
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
CA21765/CA/NCI NIH HHS; R01 GM062896/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Phosphatidylethanolamines; 0/RNA, Messenger; 0/Triglycerides; 39382-08-6/phosphatidylethanolamine; 5KV86114PT/Ethanolamine; 63-38-7/Cytidine Diphosphate; EC 2.7.7.-/RNA Nucleotidyltransferases; EC 2.7.7.14/Ethanolamine-phosphate cytidylyltransferase
Comments/Corrections

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


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