A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(-/-) mice

Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13995-4000. doi: 10.1073/pnas.96.24.13995.


A deficiency in essential fatty acid metabolism has been reported in plasma from patients with cystic fibrosis (CF). However, its etiology and role in the expression of disease is unknown. The objective of this study was to determine whether alterations in fatty acid metabolism are specific to CF-regulated organs and whether they play a role in the expression of disease. A membrane lipid imbalance was found in ileum, pancreas, and lung from cftr(-/-) mice characterized by an increase in phospholipid-bound arachidonic acid and a decrease in phospholipid-bound docosahexaenoic acid (DHA). This lipid imbalance was observed in organs pathologically affected by CF including lung, pancreas, and ileum and was not secondary to impaired intestinal absorption or hepatic biosynthesis of DHA. As proof of concept, oral administration of DHA to cftr(-/-) mice corrected this lipid imbalance and reversed the observed pathological manifestations. These results strongly suggest that certain phenotypic manifestations of CF may result from remediable alterations in phospholipid-bound arachidonic acid and DHA levels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Arachidonic Acid / metabolism
  • Arachidonic Acid / physiology*
  • Cystic Fibrosis / pathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Docosahexaenoic Acids* / administration & dosage
  • Docosahexaenoic Acids* / metabolism
  • Ileum / metabolism
  • Ileum / pathology
  • Intestinal Absorption
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Liver / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Membrane Lipids / metabolism
  • Membrane Lipids / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pancreas / metabolism
  • Pancreas / pathology
  • Phenotype
  • Phospholipids / metabolism
  • Phospholipids / physiology*
  • Pneumonia
  • Pseudomonas / immunology


  • Lipopolysaccharides
  • Membrane Lipids
  • Phospholipids
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Docosahexaenoic Acids
  • Arachidonic Acid