title: Cell culture models demonstrate that CFTR dysfunction leads to defective fatty acid composition and metabolism.
abstract: Cystic fibrosis (CF) is associated with fatty acid alterations characterized by low linoleic and docosahexaenoic acid. It is not clear whether these fatty acid alterations are directly linked to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction or result from nutrient malabsorption. We hypothesized that if fatty acid alterations are a result of CFTR dysfunction, those alterations should be demonstrable in CF cell culture models. Two CF airway epithelial cell lines were used: 16HBE, sense and antisense CFTR cells, and C38/IB3-1 cells. Wild-type (WT) and CF cells were cultured in 10% fetal bovine serum (FBS) or 10% horse serum. Fatty acid levels were analyzed by GC-MS. Culture of both WT and CF cells in FBS resulted in very low linoleic acid levels. When cells were cultured in horse serum containing concentrations of linoleic acid matching those found in human plasma, physiological levels of linoleic acid were obtained and fatty acid alterations characteristic of CF tissues were then evident in CF compared with WT cells. Kinetic studies with radiolabeled linoleic acid demonstrated in CF cells increased conversion to longer and more-desaturated fatty acids such as arachidonic acid. In conclusion, these data demonstrate that CFTR dysfunction is associated with altered fatty acid metabolism in cultured airway epithelial cells.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersson
authors.forename: M Rabie
authors.initials: MR
authors.lastname: Al-Turkmani
authors.forename: Juanito E
authors.initials: JE
authors.lastname: Savaille
authors.forename: Ragheed
authors.initials: R
authors.lastname: Alturkmani
authors.forename: Waddah
authors.initials: W
authors.lastname: Katrangi
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Cluette-Brown
authors.forename: Munir M
authors.initials: MM
authors.lastname: Zaman
authors.forename: Michael
authors.initials: M
authors.lastname: Laposata
authors.forename: Steven D
authors.initials: SD
authors.lastname: Freedman
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics); D001980:Bronchi / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D003470:Culture Media; D003550:Cystic Fibrosis / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism / Q000494:pharmacology; D051379:Mice
chemical_list: D016375:Antisense Elements (Genetics); C505032:CFTR protein, human; D003470:Culture Media; D005227:Fatty Acids; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019787:Linoleic Acid