TY - JOUR
T1 - Phospholipid class-specific brain enrichment in response to lysophosphatidylcholine docosahexaenoic acid infusion
AU - Chouinard-Watkins, Raphaël
AU - Chen, Chuck T.
AU - Metherel, Adam H.
AU - Lacombe, R. J. Scott
AU - Thies, Frank
AU - Masoodi, Mojgan
AU - Bazinet, Richard P.
N1 - This project was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) [482597] and from the Canadian Institutes of Health Research (CIHR) [497215] to Dr. R.P. Bazinet and by a NSERC studentship to Dr. C.T. Chen.
PY - 2017/10
Y1 - 2017/10
N2 - Recent studies suggest that at least two pools of plasma docosahexaenoic acid (DHA) can supply the brain: non-esterified DHA (NE-DHA) and lysophosphatidylcholine (lysoPtdCho)-DHA. In contrast to NE-DHA, brain uptake of lysoPtdCho-DHA appears to be mediated by a specific transporter, but whether both forms of DHA supply undergo the same metabolic fate, particularly with regards to enrichment of specific phospholipid (PL) subclasses, remains to be determined. This study aimed to evaluate brain uptake of NE-DHA and lysoPtdCho-DHA into brain PL classes. Fifteen-week old rats were infused intravenously with radiolabelled NE-14C-DHA or lysoPtdCho-14C-DHA (n = 4/group) over five mins to achieve a steady-state plasma level. PLs were extracted from the brain and separated by thin layer chromatography and radioactivity was quantified by liquid scintillation counting. The net rate of entry of lysoPtdCho-DHA into the brain was between 62% and 85% lower than the net rate of entry of NE-DHA, depending on the PL class. The proportion of total PL radioactivity in the lysoPtdCho-14C-DHA group compared to the NE-14C-DHA group was significantly higher in choline glycerophospholipids (ChoGpl) (48% vs 28%, respectively) but lower in ethanolamine glycerophospholipids (EtnGpl) (32% vs 46%, respectively). In both groups, radioactivity was disproportionally high in phosphatidylinositol and ChoGpl but low in phosphatidylserine and EtnGpl compared to the corresponding DHA pool size. This suggests that DHA undergoes extensive PL remodeling after entry into the brain.
AB - Recent studies suggest that at least two pools of plasma docosahexaenoic acid (DHA) can supply the brain: non-esterified DHA (NE-DHA) and lysophosphatidylcholine (lysoPtdCho)-DHA. In contrast to NE-DHA, brain uptake of lysoPtdCho-DHA appears to be mediated by a specific transporter, but whether both forms of DHA supply undergo the same metabolic fate, particularly with regards to enrichment of specific phospholipid (PL) subclasses, remains to be determined. This study aimed to evaluate brain uptake of NE-DHA and lysoPtdCho-DHA into brain PL classes. Fifteen-week old rats were infused intravenously with radiolabelled NE-14C-DHA or lysoPtdCho-14C-DHA (n = 4/group) over five mins to achieve a steady-state plasma level. PLs were extracted from the brain and separated by thin layer chromatography and radioactivity was quantified by liquid scintillation counting. The net rate of entry of lysoPtdCho-DHA into the brain was between 62% and 85% lower than the net rate of entry of NE-DHA, depending on the PL class. The proportion of total PL radioactivity in the lysoPtdCho-14C-DHA group compared to the NE-14C-DHA group was significantly higher in choline glycerophospholipids (ChoGpl) (48% vs 28%, respectively) but lower in ethanolamine glycerophospholipids (EtnGpl) (32% vs 46%, respectively). In both groups, radioactivity was disproportionally high in phosphatidylinositol and ChoGpl but low in phosphatidylserine and EtnGpl compared to the corresponding DHA pool size. This suggests that DHA undergoes extensive PL remodeling after entry into the brain.
KW - Brain
KW - docosahexaenoic acid
KW - lysophosphatidylcholine
KW - phosphatidylcholine
KW - phosphatidylethanolamine
KW - phosphatidylserine
U2 - 10.1016/j.bbalip.2017.07.013
DO - 10.1016/j.bbalip.2017.07.013
M3 - Article
C2 - 28760485
VL - 1862
SP - 1092
EP - 1098
JO - Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids
SN - 1388-1981
IS - 10, Part A
ER -