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.
Pifferi
F
F
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.
Jouin
M
M
Alessandri
J M
JM
Haedke
U
U
Roux
F
F
Perrière
N
N
Denis
I
I
Lavialle
M
M
Guesnet
P
P
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