No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF phenotype. To establish whether cystic fibrosis transmembrane conductance regulator (CFM) dysfunction affects LCPUFA synthesis, we quantified EFA metabolism in cftr(-/-CAM) and cftr(+/+CAM) mice. Effects of intestinal phenotype, diet, age, and genetic background on EFA status were evaluated in cftr(-/-CAM) mice, DeltaF508/DeltaF508 mice, and litter-mate controls. EFA metabolism was measured by C-13 stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr(-/-CAM) mice, DeltaF508/DeltaF508 mice, littermate controls, and C57B1/6 wild types fed chow or liquid diet. After enteral administration of [C-13]EFA, arachidonic acid (AA) and docosahexaenoic acid (DRA) were equally C-13-enriched in cftr(-/-CAM) and cftr(+/+CAM) mice, indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr(-/-CAM) and DeltaF508/DeltaF508 mice and controls. LCPUFA levels were also equal in liquid diet-weaned cftr(-/-CAM) mice and littermate controls, but consistently higher than in age- and diet-matched C57B1/6 wild types. We conclude that cftr(-/-CAM) mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably linked to the CF genotype. EFA status in murine CF models is strongly determined by genetic background.-Werner, A., M. E. J. Bongers, M. J. Bijvelds, H. R. de Jonge, and H. J. Verkade. No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis.