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

• Main Authors: Anniek Werner, Marloes E.J. Bongers, Marcel J. Bijvelds, Hugo R. de Jonge, Henkjan J. Verkade
• Format: Article
• Language: English
• Published: Elsevier 2004-12-01
• Series: Journal of Lipid Research
• Subjects: arachidonic acid; cystic fibrosis transmembrane conductance regulator; docosahexaenoic acid; essential fatty acid deficiency; α-linolenic acid; linoleic acid
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520341080

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 (CFTR) 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, ΔF508/ΔF508 mice, and littermate controls. EFA metabolism was measured by 13C stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr−/−CAM mice, ΔF508/ΔF508 mice, littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After enteral administration of [13C]EFA, arachidonic acid (AA) and docosahexaenoic acid (DHA) were equally 13C-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 ΔF508/ΔF508 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 C57Bl/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.