A Mechanism Accounting for the Low Cellular Level of Linoleic Acid in Cystic Fibrosis and Its Reversal by DHA

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2008 May 16

PMID 18480495

Citations 20

Authors

M Rabie Al-Turkmani

Charlotte Andersson

Ragheed Alturkmani

Waddah Katrangi

Joanne E Cluette-Brown

Steven D Freedman

Michael Laposata

Affiliations

Soon will be listed here.

Abstract

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18:3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementation.

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