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

32 Scopus citations

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 1 2008
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Fingerprint Dive into the research topics of 'A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA'. Together they form a unique fingerprint.

  • 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