Role for animal models in understanding essential fatty acid deficiency in cystic fibrosis

Cell Mol Life Sci. 2021 Dec;78(24):7991-7999. doi: 10.1007/s00018-021-04014-2. Epub 2021 Nov 5.


Essential fatty acid deficiency has been observed in most patients with Cystic Fibrosis (CF); however, pancreatic supplementation does not restore the deficiency, suggesting a different pathology independent of the pancreas. At this time, the underlying pathological mechanisms are largely unknown. Essential fatty acids are obtained from the diet and processed by organs including the liver and intestine, two organs significantly impacted by mutations in the cystic fibrosis transmembrane conductance regulator gene (Cftr). There are several CF animal models in a variety of species that have been developed to investigate molecular mechanisms associated with the CF phenotype. Specifically, global and systemic mutations in Cftr which mimic genotypic changes identified in CF patients have been generated in mice, rats, sheep, pigs and ferrets. These mutations produce CFTR proteins with a gating defect, trafficking defect, or an absent or inactive CFTR channel. Essential fatty acids are critical to CFTR function, with a bidirectional relationship between CFTR and essential fatty acids proposed. Currently, there are limited analyses on the essential fatty acid status in most of these animal models. Of interest, in the mouse model, essential fatty acid status is dependent on the genotype and resultant phenotype of the mouse. Future investigations should identify an optimal animal model that has most of the phenotypic changes associated with CF including the essential fatty acid deficiencies, which can be used in the development of therapeutics.

Keywords: Animal models; Arachidonic acid; Cftr; Cystic fibrosis; Docosahexaenoic acid; Essential fatty acid; Linoleic acid.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified*
  • Cystic Fibrosis / etiology
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / pathology*
  • Disease Models, Animal*
  • Fatty Acids, Essential / deficiency*
  • Humans
  • Ion Transport
  • Phenotype*


  • Fatty Acids, Essential