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Originally published In Press as doi:10.1194/jlr.M700386-JLR200 on October 11, 2007

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Journal of Lipid Research, Vol. 49, 147-152, January 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

The low density lipoprotein receptor is not necessary for maintaining mouse brain polyunsaturated fatty acid concentrations

Chuck T. Chen*, David W. L. Ma1,*, John H. Kim{dagger}, Howard T. J. Mount{dagger} and Richard P. Bazinet2,*

* Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
{dagger} Departments of Medicine (Division of Neurology) and Physiology, Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada

Published, JLR Papers in Press, October 11, 2007.

1 Current address of D. W. L. Ma: Department of Human Health and Nutritional Sciences, College of Biological Science, University of Guelph, Guelph, Ontario, Canada.

2 To whom correspondence should be addressed. e-mail: richard.bazinet{at}utoronto.ca

The brain cannot synthesize n-6 or n-3 PUFAs de novo and requires their transport from the blood. Two models of brain fatty acid uptake have been proposed. One requires the passive diffusion of unesterified fatty acids through endothelial cells of the blood-brain barrier, and the other requires the uptake of lipoproteins via a lipoprotein receptor on the luminal membrane of endothelial cells. This study tested whether the low density lipoprotein receptor (LDLr) is necessary for maintaining brain PUFA concentrations. Because the cortex has a low basal expression of LDLr and the anterior brain stem has a relatively high expression, we analyzed these regions separately. LDLr knockout (LDLr–/–) and wild-type mice consumed an AIN-93G diet ad libitum until 7 weeks of age. After microwaving, the cortex and anterior brain stem (pons and medulla) were isolated for phospholipid fatty acid analyses. There were no differences in phosphatidylserine, phosphatidylinositol, ethanolamine, or choline glycerophospholipid esterified PUFA or saturated or monounsaturated fatty acid concentrations in the cortex or brain stem between LDLr–/– and wild-type mice. These findings demonstrate that the LDLr is not necessary for maintaining brain PUFA concentrations and suggest that other mechanisms to transport PUFAs into the brain must exist.

Supplementary key words arachidonic acid • docosahexaenoic acid • transport • knockout

Abbreviations: 16:0, palmitic acid; 18:2n-6, linoleic acid; 18:3n-3, {alpha}-linolenic acid; 20:4n-6, arachidonic acid; 22:6n-3, docosahexaenoic acid; CerPCho, sphingomyelin; ChoGpl, choline glycerophospholipid; EtnGpl, ethanolamine glycerophospholipid; LDLr, low density lipoprotein receptor; PtdIns, phosphatidylinositol; PtdSer, phosphatidylserine


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