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

David W.L. Ma,John H. Kim,Howard T.J. Mount,Richard P. Bazinet,Chuck T. Chen

doi:10.1194/jlr.m700386-jlr200

David W.L. Ma, John H. Kim + Show 3 more

Open Access

https://doi.org/10.1194/jlr.m700386-jlr200

Copy DOI

Abstract

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.

Highlights

The brain cannot synthesize n-6 or n-3 PUFAs de novo and requires their transport from the blood
Because cholesterol is not transported from LDL into the brain [38], it was further suggested that the low density lipoprotein receptor (LDLr) is expressed on the luminal membrane of endothelial cells and is absent from the abluminal membrane [27]
The cortex and brain stem phospholipid esterified fatty acid concentrations from wild-type mice in this study are similar to literature values [45, 51], and slight discrepancies are likely attributable to differences in diet and brain region analyses [1, 52]. 20:4n-6 from the plasma unesterified pool is rapidly esterified to choline glycerophospholipid (ChoGpl) and PtdIns [51, 53], whereas 22:6n-3 is rapidly esterified to ethanolamine glycerophospholipid (EtnGpl) and ChoGpl [54, 55]

Summary

Introduction

The brain cannot synthesize n-6 or n-3 PUFAs de novo and requires their transport from the blood. This study tested whether the low density lipoprotein receptor (LDLr) is necessary for maintaining brain PUFA concentrations. 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 LDLr2/2 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.—Chen, C. LDL would be taken up by the LDLr on the luminal membrane and hydrolyzed within endothelial cells, allowing unesterified fatty acids, but not intact, cholesterolcontaining lipoproteins, to enter the brain parenchyma [27]

Methods

Results

Conclusion