DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity

Sarah W. Njoroge, Michael Laposata, Waddah Katrangi, Adam C. Seegmiller

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)257-265
Number of pages9
JournalJournal of Lipid Research
Volume53
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Keywords

  • Docosapentaenoate
  • Eicosapentaenoate
  • Fatty acid metabolism
  • Gene expression
  • Omega-3 fatty acids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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