Interactions of linoleic and alpha-linolenic acids in the development of fatty acid alterations in cystic fibrosis

Patients with cystic fibrosis (CF) exhibit characteristic polyunsaturated fatty acid abnormalities, including low linoleic acid and high arachidonic acid levels that are thought to contribute to the pathophysiology of this disease. Recent studies indicate that changes in fatty acid metabolism are responsible for these abnormalities. This study examines the role of fatty acid substrate concentrations in the development of these alterations in a cultured cell model of CF. By incubating cells with varying concentrations of exogenous fatty acids, it shows that increasing the concentration of substrates from the parallel n-3 and n-6 polyunsaturated fatty acid pathways (linoleic acid and alpha-linolenic acid, respectively) not only increases formation of the products in that pathway, but also reduces metabolism in the parallel pathway. In particular, we demonstrate that high levels of linoleic acid and low levels of alpha-linolenic acid are required to observe the typical fatty acid alterations of cystic fibrosis. These results shed light on the mechanisms of fatty acid metabolic abnormalities in cystic fibrosis. They also have implications for the nutritional therapy of CF, highlighting the importance of specific fatty acid content, and in understanding the anti-inflammatory effects of n-3 fatty acids.