Brain arachidonic acid incorporation is decreased in heart fatty acid binding protein gene-ablated mice.
Heart fatty acid binding protein (H-FABP) is expressed in neurons, but its role in brain fatty acid incorporation and metabolism is poorly defined. We examined the effect of H-FABP gene ablation on brain incorporation of arachidonic ([1-(14)C]20:4n-6) or palmitic ([1-(14)C]16:0) acid in vivo. Analysis of brain mRNA confirmed gene ablation and demonstrated no compensatory changes in the levels of other FABP mRNA in the gene-ablated mice. In brains from H-FABP gene-ablated mice, the incorporation coefficient for [1-(14)C]20:4n-6 was reduced 24%, while that for [1-(14)C]16:0 was unaffected. Within the organic and aqueous fractions, significantly more [1-(14)C]20:4n-6 was distributed into the aqueous fraction, suggesting a disruption in the metabolic targeting of 20:4n-6 in these mice. There was less incorporation of [1-(14)C]20:4n-6 into total phospholipids and a marked reduction (51%) in the level of incorporation into the choline glycerophospholipids (ChoGpl). Because FABP can influence steady-state lipid mass, brain individual lipid masses were measured. The brain total phospholipid mass was reduced 17% by gene ablation, ascribed to a 27% and 32% reduction in the masses of ChoGpl and sphingomyelin, respectively. Plasmalogen subclass masses were also reduced, suggesting that H-FABP may augment brain plasmalogen synthesis. In gene-ablated mice, the phosphatidylinositol 20:4n-6 level was reduced 25%, while the proportion of total n-6 fatty acids was reduced in the major phospholipid classes. Thus, these results demonstrate for the first time that H-FABP expression influences brain 20:4n-6 uptake and trafficking as well as steady-state brain lipid levels.
Murphy
Eric J
EJ
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, North Dakota 58202-9037, USA. emurphy@medicine.nodak.edu
Owada
Yuji
Y
Kitanaka
Noriko
N
Kondo
Hisatake
H
Glatz
Jan F C
JF
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D010955:Plasmalogens / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D010743:Phospholipids; D010955:Plasmalogens; D012333:RNA, Messenger; D016718:Arachidonic Acid; D004247:DNA