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.
Highlights
Cystic fibrosis (CF) is associated with fatty acid alterations characterized by low linoleic and docosahexaenoic acid
Cells cultured in horse serum lot B to assess for variability in fatty acid composition of the media resulted in lower linoleic acid levels than in horse serum lot A
The presence of fatty acid alterations in this model of cultured CF airway epithelial cells clearly establishes that loss of cystic fibrosis transmembrane conductance regulator (CFTR) function, either through antisense suppression or through CFTR gene mutations, is associated with alterations in fatty acid composition
Summary
Cystic fibrosis (CF) is associated with fatty acid alterations characterized by low linoleic and docosahexaenoic acid. Fatty acid levels were analyzed by GC-MS Culture of both WT and CF cells in FBS resulted in very low linoleic acid levels. Kinetic studies with radiolabeled linoleic acid demonstrated in CF cells increased conversion to longer and more-desaturated fatty acids such as arachidonic acid These data demonstrate that CFTR dysfunction is associated with altered fatty acid metabolism in cultured airway epithelial cells.—Andersson, C., M. Further studies have described low serum levels of docosahexaenoic acid (DHA) and increased serum levels of palmitoleic acid in CF patients [5] accompanied by altered turnover of essential fatty acids in CF cells [6, 7].
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