A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(-/-) mice

A deficiency in essential fatty acid metabolism has been reported in plasma from patients with cystic: fibrosis (CF), However, its etiology and role i n the expression of disease is unknown. The objective of this study was to determine whether alterations in fatty acid metabolism are specific to CF-r egulated organs and whether they play a role in the expression of disease. A membrane lipid imbalance was found in ileum, pancreas, and lung from cftr (-/-) mice characterized by an increase in phospholipid-bound arachidonic a cid and a decrease in phospholipid-bound docosahexaenoic acid (DHA). This l ipid imbalance was observed in organs pathologically affected by CF includi ng lung, pancreas, and ileum and was not secondary to impaired intestinal a bsorption or hepatic biosynthesis of DHA. As proof of concept, oral adminis tration of DHA to cftr(-/-) mice corrected this lipid imbalance and reverse d the observed pathological manifestations. These results strongly suggest that certain phenotypic manifestations of CF may result from remediable alt erations in phospholipid-bound arachidonic acid and DHA levels.