Cell culture models demonstrate that CFTR dysfunction leads to defective fatty acid composition and metabolism

Charlotte Andersson, M. Rabie Al-Turkmani, Juanito E. Savaille, Ragheed Alturkmani, Waddah Katrangi, Joanne E. Cluette-Brown, Munir M. Zaman, Michael Laposata, and Steven D. Freedman

Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215

Corresponding Author: canderss{at}bidmc.harvard.edu

Cystic fibrosis (CF) is associated with fatty acid alterations characterized by low linoleic and docosahexaenoic acid. It is not clear if these fatty acid alterations are directly linked to CFTR dysfunction or are resulting 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 and CF cells were cultured in 10% FBS or 10% horse serum. Fatty acid levels were analyzed by GC/MS. Culture of both wild type 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 now evident in CF compared to wild type 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.

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