Lipidome Alterations Induced by Cystic Fibrosis, CFTR Mutation, and Lung Function

J Proteome Res. 2021 Jan 1;20(1):549-564. doi: 10.1021/acs.jproteome.0c00556. Epub 2020 Oct 22.


Cystic fibrosis is a genetic pathology characterized by abnormal accumulation of mucus in the respiratory, gastrointestinal, and reproductive tracts, caused by mutations in the CFTR gene. Although the classical presentation of the condition is well known, there is still a need for a better characterization of metabolic alterations related to cystic fibrosis and different genotypic mutations. We employed untargeted, comprehensive lipidomics of blood serum samples to investigate alterations in the lipid metabolism related to the pathology, mutation classes, and lung function decline. Six unique biomarker candidates were able to independently differentiate diseased individuals from healthy controls with excellent performance. Cystic fibrosis patients showed dyslipidemia for most lipid subclasses, with significantly elevated odd-chain and polyunsaturated fatty acyl lipids. Phosphatidic acids and diacylglycerols were particularly affected by different genotypic mutation classes. We selected a biomarker panel composed of four lipids, including two ceramides, one sphingomyelin, and one fatty acid, which correctly classified all validation samples from classes III and IV. A biomarker panel of five oxidized lipids was further selected to differentiate patients with reduced lung function, measured as predicted FEV1%. Our results indicate that cystic fibrosis is deeply related to lipid metabolism and provide new clues for the investigation of the disease mechanisms and therapeutic targets.

Keywords: CFTR genotype; FEV1percent; biomarker; blood serum; cystic fibrosis; lipidomics; lung function; odd-chain fatty acid; phosphatidic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / genetics
  • Humans
  • Lipidomics*
  • Lung / physiopathology
  • Mutation


  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator

Grant support