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Journal of Lipid Research, Vol. 49, 1692-1700, August 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

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^1,*

^* Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114

^* This study was funded by National Institutes of Health Grant R01 DK-52765 (S.D.F.) and The Cystic Fibrosis Foundation (FREEDM06A0).

Published, JLR Papers in Press, April 25, 2008.

¹To whom correspondence should be addressed. e-mail: sfreedma{at}bidmc.harvard.edu

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.

Supplementary key words cystic fibrosis transmembrane conductance regulator • essential fatty acid deficiency • fetal bovine serum • horse serum • arachidonic acid • docosahexaenoic acid • confluence • 6-desaturase

Abbreviations: AA, arachidonic acid; CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FAME, fatty acid methyl ester; FBS, fetal bovine serum; WT, wild type

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