Document Detail


DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity.
MedLine Citation:
PMID:  22095831     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients and models of cystic fibrosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturases. These abnormalities and the consequent CF-related pathologic manifestations can be reversed in CF mouse models by dietary supplementation with DHA. However, the mechanism is unknown. This study investigates this mechanism by measuring the effect of exogenous DHA and eicosapentaenoate (EPA) supplementation on fatty acid composition and metabolism, as well as on metabolic enzyme expression, in a cell culture model of CF. We found that both DHA and EPA suppress the expression and activity of Δ5- and Δ6-desaturases, leading to decreased flux through the n-3 and n-6 PUFA metabolic pathways and decreased production of AA. The findings also uncover other metabolic abnormalities, including increased fatty acid uptake and markedly increased retroconversion of DHA to EPA, in CF cells. These results indicate that the fatty acid abnormalities of CF are related to intrinsic alterations of PUFA metabolism and that they may be reversed by supplementation with DHA and EPA.
Authors:
Sarah W Njoroge; Michael Laposata; Waddah Katrangi; Adam C Seegmiller
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-16
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-10     Completed Date:  2012-08-27     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  257-65     Citation Subset:  IM    
Affiliation:
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Cystic Fibrosis / diet therapy,  metabolism*,  pathology
Dietary Supplements
Docosahexaenoic Acids / metabolism,  pharmacology*
Eicosapentaenoic Acid / metabolism,  pharmacology*
Epithelial Cells / drug effects,  metabolism
Fatty Acid Desaturases / genetics,  metabolism*
Fatty Acids / metabolism*
Fatty Acids, Omega-3 / metabolism
Fatty Acids, Omega-6 / metabolism
Humans
Linoleoyl-CoA Desaturase / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Fatty Acids, Omega-3; 0/Fatty Acids, Omega-6; 1553-41-9/Eicosapentaenoic Acid; 25167-62-8/Docosahexaenoic Acids; EC 1.14.19.-/Fatty Acid Desaturases; EC 1.14.19.3/Linoleoyl-CoA Desaturase; EC 1.14.99.-/delta-5 fatty acid desaturase
Comments/Corrections

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


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