C]DHA in phosphatidylcholine

The amount and distribution of [ 13 C]docosahexaenoic acid (DHA) in plasma, platelet, and erythrocyte lipid classes were followed as a function of time (1 to 72 h) in young adults after ingestion of a single dose of [ 13 C]DHA esterified in a phosphatidylcholine (PC), in using gas chromatography combustion–isotope ratio mass spectrometry. [ 13 C]DHA first appeared in plasma non-esterified fatty acids (NEFA) and triglycerides (TG), with a maximal appearance at 6 h and a further decline, then being delayed 3-fold compared to [ 13 C]DHA ingested in triglycerides. Lysophosphatidylcholine (LPC) was also enriched in [ 13 C]DHA, due mainly to earlier hepatic secretion, and plateaued at 6 h, whereas phosphatidylethanolamine (PE) and phosphatidylcholine (PC) containing [ 13 C]DHA plateaued at 9 h. The labeling of erythrocyte and platelet phospholipids exhibited different kinetics, probably involving different metabolic pathways for [ 13 C]DHA incorporation in cell membranes. Computation of the relative contribution of LPC and NEFA for delivery of [ 13 C]DHA to blood cells showed that the supply to platelets occurred through NEFA. In contrast, [ 13 C]DHA was carried by both LPC and NEFA to erythrocytes, which differs from what was previously been observed after intake of triglycerides labeled with [ 13 C]DHA where LPC was the only source of [ 13 C]DHA for erythrocytes. We conclude that the lipid form of ingested DHA affects markedly its kinetics and partly its metabolic fate. —LemaitreDelaunay, D., C. Pachiaudi, M. Laville, J. Pousin, M. Armstrong, and M. Lagarde. Blood compartmental metabolism of docosahexaenoic acid (DHA) in humans after ingestion of a single dose of [ 13 C]DHA in phosphatidylcholine. J. Lipid Res. 1999. 40: 1867–1874. Supplementary key words docosahexaenoic acid • stable isotope • plasma • platelets • erythrocytes Marine oils, which contain high levels of polyunsaturated fatty acids (PUFA) of the n–3 family such as docosahexaenoic (DHA, 22:6n–3) and eicosapentaenoic (EPA, 20:5n–3) acids (1), may have beneficial roles in the prevention of cardiovascular diseases (2, 3). N–3 PUFA exert antiatherothrombotic effects through modulation of blood lipids (4) and lipoproteins (5). Furthermore, it has been found that long chain polyunsaturated n–3 fatty acids could decrease plasma triglyceride levels (6) and cause a prolongation of bleeding time. The incorporation of n–3 PUFA in cell membranes also modifies eicosanoid production resulting in altered platelet and leukocyte reactivities (7, 8). DHA, a minor component of human plasma lipids, is a major fatty acid of phospholipids in the brain and retina (9). This fatty acid is required for the development of visual acuity and learning in humans (10, 11). Although the biological properties of DHA have been documented, the mechanisms by which this fatty acid is taken up by the brain and blood cells, the pathway of its absorption, and its transport and dynamic exchanges within blood lipid pools for the assimilation by human tissues remain largely unknown. Lysophosphatidylcholine (LPC), a second form of blood phospholipid (12), could be a transport system for PUFA (13) when secreted by the liver and could enhance the PUFA absorption and distribution (14). The transport of DHA to target cells has been reported in humans after a single ingestion of this 13 C-labeled fatty acid esterified in triglycerides (15). It has been shown that plasma albumin carries DHA in two forms, as non-esterified fatty acids (NEFA) which supply this fatty acid to platelets, and as LPC which delivers it to erythrocytes. The mechanism of cellular uptake of fatty acids presumably involves a carrier-mediated and a passive transmembrane translocation (16). On the other hand, the uptake of PUFA by red Abbreviations: BHT, butylated hydroxytoluene; CE, cholesterol ester; DHA, docosahexaenoic acid; GCC-IRMS, gas-chromatography combustion–isotope ratio mass spectrometry; GLC, gas–liquid chromatography; HPLC, high performance liquid chromatography; LCAT, lecithin:cholesterol acyltransferase; LPC, lysophosphatidylcholine; NEFA, non-esterified fatty acids; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PL, phospholipids; TG, triglycerides. 1 To whom correspondence should be addressed. at P E N N S T A T E U N IV E R S IT Y , on F ebuary 2, 2013 w w w .j.org D ow nladed fom