INCORPORATION OF DIETARY 5,11,14-ICOSATRIENOATE INTO VARIOUS MOUSE PHOSPHOLIPID CLASSES AND TISSUES

To investigate the basis of acyl specificity in the phosphatidylinositol (PI) lipid class, we fed mice fatty acids lacking the usual methylene interrupted double bonds. Mice were fed 10 wt% diets containing either 2.9 or 16% 5,11,14-icosatrienoate (5,11,14-20:3) as a component of seed oil mixtures, or control oil mixtures in which either 18:1n-9 or 18:3n-3 replaced the 5,11,14-20:3 content of the seed oils, for a 2-week period. 5,11,14-20:3 was found to be maximally incorporated into cardiac and hepatic PI (15-17 area%), and hepatic phosphatidylcholine (13%), but minimally incorporated into neutral lipids and those phospholipids that contain small amounts of 20:4n-6, such as hepatic sphingomyelin and cardiolipin. Within the PI class, there were important differences in the tissue distribution of 5,11,14-20:3: liver>heart>kidney = spleen>thymus = visceral fat. There was a clear selectivity for the incorporation of this fatty acid into PI as compared with other phospholipids. 5,11,14-20:3 was also extensively incorporated into hepatic phosphatidylinositol bisphosphate (PIP2), a precursor of second messengers. In hepatic PI, 5,11,14-20:3 replaced 20:4n-6, resulting in a 50% reduction in the level of 20:4n-6. By contrast, in phosphatidylcholine and phosphatidylethanolamine lipid classes, 5,11,14-20:3 replaced several polyenes, including 18:2n-6, 20:4n-6, and 20:5n-3. In comparison with dietary 18:3n-3, 5,11,14-20:3 was found to be more effective at decreasing hepatic PI 20:4n-6 levels. Because leukotrienes and prostaglandins cannot be formed from 5,11,14-20:3 due to the lack of an internal DELTA8 double bond, and because 20:4n-6 was dramatically reduced in some PI pools, we expect that 5,11,14-20:3 may alter eicosanoid signaling.