Fatty acid desaturation in lung: inhibition by unsaturated fatty acids1

The activity of the enzyme system involved in desaturation of palmitic and stearic acid has been examined in lungs of rats fed fat-free diets supplemented either with 4% safflower oil (controls) or 4% tripalmitin (essential fatty acid (EFA) deficient) both in vivo and in vitro in lung slices. Desaturation, as measured by appearance of '*C-labeled monounsaturated fatty acid in pulmonary total lipid and phospholipids, was significantly greater in vivo and in vitro in lung tissue from EFA-deficient rats. In vitro preincubation of lung slices for 1 to 4 hr with 1 mM oleic, linoleic, or linolenic acid reduced the extent of desaturation of [ 1-I4C]stearic acid significantly in both dietary groups, but the effect was greater in EFA-deficient tissues. The effect of linoleic acid was always greater than that of oleic acid. Preincubation with palmitic acid and 16,16-dimethyl PGE, was without effect. Thus: 1) EFA deficiency has been shown to enhance desaturation of palmitic and stearic acid in lung; 2) in vitro addition of linoleic or linolenic acid inhibited desaturation significantly; and 3) oleic acid was inhibitory but to a lesser and more variable extent. Palmitic acid was not inhibitory.-Baht, J. A., E. C. Kyriakides, and D. A. Beeler. Fatty acid desaturation in lung: inhibition by unsaturated fatty acids.]. Lipid Res. 1980. 21: 868-873. Supplementary key words oleate . linoleate . palmitate ' prostaglandin * linolenate We have demonstrated that in rats fed diets deficient in essential fatty acids (EFA) there is a decreased content of disaturated phosphatidylcholine in lung tissue and lung lavage material, while the content of total phosphatidylcholine (PC) is not altered (1). Refeeding a similar diet supplemented with 4% by weight of safflower oil, rich in linoleate, led to reversal of these changes in 3-7 days (1). The changes produced by EFA deficiency in lung PC fatty acid composition are similar to those seen in premature infants who are at a high risk for developing the respiratory distress syndrome (2-4). The alterations in lung PC induced by EFA deficiency are associated with impaired lung stability and reduced surface tension lowering ability of lung lavage PC (5) . Previous work by others has demonstrated that feeding of diets supplemented with linoleate reduces the activity of A 9 desaturase in liver (6, 7). Montgomery (8) has reported the presence of A 9 desaturase activity in lung microsomes, and showed that this activity was enhanced by feeding a fat-free diet for 4 days. T h e present experiments were therefore undertaken with two main objectives in mind: 1) to determine whether EFA deficiency was associated with increased activity of A 9 desaturase in lung tissue, and 2) to examine the effects of in vitro incubation of lung tissue with oleic, linoleic, or linolenic acids on the activity of this enzyme system. METHODS AND MATERIALS