The metabolic fate of docosahexaenoic acid (DHA) was evaluated from its intake as a nutrient in triglycerides and phosphatidylcholines to its uptake by target tissues, especially the brain. Several approaches were used including the kinetics and tissue distribution of ingested 13C-labeled DHA, the incorporation of radiolabeled DHA injected as its nonesterified form compared to the fatty acid esterified in lysophosphatidylcholine (lysoPC), and the capacity of the two latter forms to cross a reconstituted blood-brain barrier (BBB) consisting of cocultures of brain-capillary endothelial cells and astrocytes. The results obtained allow us to raise the hypothesis that lysoPC may represent a preferred physiological carrier of DHA to the brain.

Unsaturated lysophosphatidylcholines (lysoPtdCho) bound to albumin circulate in blood plasma and seem to be a novel transport system for carrying polyunsaturated fatty acids (PUFA) to tissues that are rich in these fatty acids, such as the brain. The potential of these lysoPtdCho as a significant source of PUFA for cells has been assessed by comparing their plasma concentration with that of unsaturated non-esterified fatty acids (NEFA) bound to albumin. In humans, the PUFA concentration was 25.9+/-3.1 nmol/ml for these lysoPtdCho, compared with 33.4+/-9.6 nmol/ml for NEFA; in rats the equivalent values are 14.2+/-0.6 and 13.1+/-1.1 nmol/ml respectively (means+/-S.E.M.). The lysoPtdCho arachidonic acid content was 2-fold (human) and 5-fold (rat) higher than that of NEFA. In human and rat plasma, unsaturated lysoPtdCho were associated mainly with albumin rather than lipoproteins. The rate and extent of the acyl group shift from the sn-2 to sn-1 position of these lysoPtdCho were studied by the incubation of 1-lyso, 2-[(14)C]C(18:2)n-6-glycerophosphocholine (GPC) with plasma. The rapid isomerization of this lipid occurred at pH 7 (20% isomerization within 2 min) and was not prevented by its association with albumin. The position of the acyl group in the lysoPtdCho circulating in plasma was studied by collecting blood directly in organic solvents containing 1-lyso,2-[(14)C]C(18:2)n-6-GPC as a marker of isomerization that occurred during sampling and analysis. Approx. 50% of the PUFA was located at the sn-2 position, demonstrating that substantial concentrations of 2-acyl-lysoPtdCho are present in plasma and are available for tissue uptake, where they can be reacylated at the sn-1 position to form membrane phospholipids.

The apparent retroconversion of docosahexaenoic acid (22:6n-3) to eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) was studied in vivo, in rats and humans, after they ingested a single dose of triacylglycerols containing [13C]22:6n-3 ([13C]22:6-triacylglycerol), without 22:6n-3 dietary supplementation. The amount of apparent retroconversion and the distribution of the three n-3 polyunsaturated fatty acids (PUFAs) in plasma lipid classes were followed as a function of time by measuring the appearance of 13C in these PUFAs with gas-chromatography combustion-isotope ratio mass spectrometry. This [13C]22:6n-3 retroconversion, calculated by summing the amounts of [13C]22:5n-3 and [13C]20:5n-3 in plasma lipids, was lower in humans than in rats, reaching a maximum of approximately 9% of the total plasma [13C]22:6n-3 in rats, but only 1.4% in humans. The incorporation of [13C]22:6n-3 and [13C]22:5n-3 in lipid classes followed their endogenous distribution with a maximal accumulation in phospholipids, but a low incorporation into cholesterol esters (CEs), whereas [13C]20:5n-3 was equally present in phospholipids and CEs. The ratio of the amount of HDL-CE to HDL-phosphatidylcholine for [13C]20:5n-3 was higher than for [13C]22:6n-3, indicating a selectivity of the lecithin-cholesterol acyltransferase enzyme with regard to these PUFAs, which may be related to the differences in their biological properties after fish oil feeding. The occurrence of a weak basal 22:6n-3 retroconversion in humans supports feeding this pure PUFA in cases in which 20:5n-3 presents undesirable side effects and when specific alterations of blood lipids are expected.