Cystic fibrosis fatty acid imbalance is linked to ceramide deficiency and corrected by fenretinide

Am J Respir Cell Mol Biol. 2009 Jul;41(1):100-6. doi: 10.1165/rcmb.2008-0279OC. Epub 2008 Dec 4.


Patients with cystic fibrosis (CF) and Cftr-knockout mice (CF mice) display an imbalance in fatty acids, with high arachidonic acid (AA) and low docosahexaenoic acid (DHA) concentrations. Our recent studies demonstrated defects in another class of lipids, ceramides, in patients with CF and in CF mice. This study investigates the relationship between ceramide, AA, DHA, and the correction of lipid imbalances in CF mice after treatment with fenretinide. Concentrations of AA, DHA, and ceramide were assessed in plasma from 58 adult patients with CF and 72 healthy control subjects. After 28 days of treatment with fenretinide, the same analysis was performed in wild-type and CF mice from plasma and organs (lung, ileum, pancreas, and liver). Low ceramide levels were associated with high AA and low DHA concentrations in patients with CF. No correlation was observed in healthy control subjects. Greater deficiencies were seen in patients with CF who were diagnosed before the age of 18, specifically with statistically significant higher levels of AA. Treatment with fenretinide (N-(4-hydroxyphenyl)retinamide; 4-HPR) normalized high levels of AA and low levels of ceramide, and increased the levels of DHA in CF mice. As in patients with CF, low ceramide levels correlated with higher AA and lower DHA levels in plasma of CF mice. Lipid abnormalities correlated with ceramide deficiencies in patients with CF and CF mice. We found that fenretinide treatment normalizes the fatty acid imbalance in CF mice with reducing AA to WT levels and increasing DHA. We propose that fenretinide treatment might improve this pathological phenotype in patients with CF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Arachidonic Acid / blood*
  • Case-Control Studies
  • Ceramides / blood
  • Ceramides / deficiency*
  • Cystic Fibrosis / blood
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis / physiopathology
  • Disease Models, Animal
  • Docosahexaenoic Acids / blood*
  • Female
  • Fenretinide / pharmacology*
  • Forced Expiratory Volume
  • Humans
  • Ileum / drug effects
  • Ileum / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / microbiology
  • Lung / physiopathology
  • Male
  • Mice
  • Mice, Inbred CFTR
  • Middle Aged
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pseudomonas Infections / blood
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / pathogenicity
  • Severity of Illness Index
  • Young Adult


  • Ceramides
  • Fenretinide
  • Docosahexaenoic Acids
  • Arachidonic Acid