A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA

M. Rabie Al-Turkmani, Charlotte Andersson, Ragheed Alturkmani, Waddah Katrangi, Joanne E. Cluette-Brown, Steven D. Freedman, Michael Laposata

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1946-1954
Number of pages9
JournalJournal of Lipid Research
Volume49
Issue number9
DOIs
StatePublished - Sep 2008
Externally publishedYes

Fingerprint

Docosahexaenoic Acids
Linoleic Acid
Cystic Fibrosis
Metabolism
Metabolites
Fatty Acids
Lipids
Lipid Metabolism
Arachidonic Acid
Phospholipids
Blood
Epithelial Cells
Cells
Tissue
Fluxes
Defects

Keywords

  • Arachidonic acid
  • Docosahexaenoic acid
  • Fatty acid alterations
  • Lipid classes
  • N-6 pathway
  • Phospholipids
  • Supplementation
  • Uptake

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Al-Turkmani, M. R., Andersson, C., Alturkmani, R., Katrangi, W., Cluette-Brown, J. E., Freedman, S. D., & Laposata, M. (2008). A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA. Journal of Lipid Research, 49(9), 1946-1954. https://doi.org/10.1194/jlr.M800035-JLR200

A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA. / Al-Turkmani, M. Rabie; Andersson, Charlotte; Alturkmani, Ragheed; Katrangi, Waddah; Cluette-Brown, Joanne E.; Freedman, Steven D.; Laposata, Michael.

In: Journal of Lipid Research, Vol. 49, No. 9, 09.2008, p. 1946-1954.

Research output: Contribution to journalArticle

Al-Turkmani, MR, Andersson, C, Alturkmani, R, Katrangi, W, Cluette-Brown, JE, Freedman, SD & Laposata, M 2008, 'A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA', Journal of Lipid Research, vol. 49, no. 9, pp. 1946-1954. https://doi.org/10.1194/jlr.M800035-JLR200
Al-Turkmani MR, Andersson C, Alturkmani R, Katrangi W, Cluette-Brown JE, Freedman SD et al. A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA. Journal of Lipid Research. 2008 Sep;49(9):1946-1954. https://doi.org/10.1194/jlr.M800035-JLR200
Al-Turkmani, M. Rabie ; Andersson, Charlotte ; Alturkmani, Ragheed ; Katrangi, Waddah ; Cluette-Brown, Joanne E. ; Freedman, Steven D. ; Laposata, Michael. / A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA. In: Journal of Lipid Research. 2008 ; Vol. 49, No. 9. pp. 1946-1954.
@article{78615c486f2f4d36a516f58a6b6fd2e0,
title = "A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA",
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.",
keywords = "Arachidonic acid, Docosahexaenoic acid, Fatty acid alterations, Lipid classes, N-6 pathway, Phospholipids, Supplementation, Uptake",
author = "Al-Turkmani, {M. Rabie} and Charlotte Andersson and Ragheed Alturkmani and Waddah Katrangi and Cluette-Brown, {Joanne E.} and Freedman, {Steven D.} and Michael Laposata",
year = "2008",
month = "9",
doi = "10.1194/jlr.M800035-JLR200",
language = "English (US)",
volume = "49",
pages = "1946--1954",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "9",

}

TY - JOUR

T1 - A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA

AU - Al-Turkmani, M. Rabie

AU - Andersson, Charlotte

AU - Alturkmani, Ragheed

AU - Katrangi, Waddah

AU - Cluette-Brown, Joanne E.

AU - Freedman, Steven D.

AU - Laposata, Michael

PY - 2008/9

Y1 - 2008/9

N2 - 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.

AB - 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.

KW - Arachidonic acid

KW - Docosahexaenoic acid

KW - Fatty acid alterations

KW - Lipid classes

KW - N-6 pathway

KW - Phospholipids

KW - Supplementation

KW - Uptake

UR - http://www.scopus.com/inward/record.url?scp=53149084542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53149084542&partnerID=8YFLogxK

U2 - 10.1194/jlr.M800035-JLR200

DO - 10.1194/jlr.M800035-JLR200

M3 - Article

C2 - 18480495

AN - SCOPUS:53149084542

VL - 49

SP - 1946

EP - 1954

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 9

ER -