n-3 Fatty acids modulate brain glucose transport in endothelial cells of the blood-brain barrier.
We have previously shown that glucose utilization and glucose transport were impaired in the brain of rats made deficient in n-3 polyunsaturated fatty acids (PUFA). The present study examines whether n-3 PUFA affect the expression of glucose transporter GLUT1 and glucose transport activity in the endothelial cells of the blood-brain barrier. GLUT1 expression in the cerebral cortex microvessels of rats fed different amounts of n-3 PUFA (low vs. adequate vs. high) was studied. In parallel, the glucose uptake was measured in primary cultures of rat brain endothelial cells (RBEC) exposed to supplemental long chain n-3 PUFA, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, or to arachidonic acid (AA). Western immunoblotting analysis showed that endothelial GLUT1 significantly decreased (-23%) in the n-3 PUFA-deficient microvessels compared to control ones, whereas it increased (+35%) in the microvessels of rats fed the high n-3 PUFA diet. In addition, binding of cytochalasin B indicated that the maximum binding to GLUT1 (Bmax) was reduced in deficient rats. Incubation of RBEC with 15 microM DHA induced the membrane DHA to increase at a level approaching that of cerebral microvessels isolated from rats fed the high n-3 diet. Supplementation of RBEC with DHA or EPA increased the [(3)H]-3-O-methylglucose uptake (reflecting the basal glucose transport) by 35% and 50%, respectively, while AA had no effect. In conclusion, we suggest that n-3 PUFA can modulate the brain glucose transport in endothelial cells of the blood-brain barrier, possibly via changes in GLUT1 protein expression and activity.
Unité de Nutrition et Régulation Lipidique des Fonctions Cérébrales (Nu.Ré.Li.Ce.), UR909 Institut National de la Recherche Agronomique (INRA), CRJ, 78352 Jouy-en-Josas Cedex, France.
F
F
Pifferi
M
M
Jouin
J M
JM
Alessandri
U
U
Haedke
F
F
Roux
N
N
Perrière
I
I
Denis
M
M
Lavialle
P
P
Guesnet
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011247:Pregnancy; D051381:Rats
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D051272:Glucose Transporter Type 1; D010714:Phosphatidylethanolamines; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D005947:Glucose