Genetic Ablation of CD36 Does not Alter Mouse Brain Polyunsaturated Fatty Acid Concentrations

Abstract

In the brain, polyunsaturated fatty acids (PUFA), especially arachidonic acid and docosahexaenoic acid (DHA), are required for regulating membrane fluidity, neuronal survival and signal transduction. Since the brain cannot synthesize n-6 and n-3 PUFA de novo, they must be supplied from the blood. However, the methods of PUFA entry into the brain are not agreed upon. This study tested the necessity of CD36, a candidate transporter of unesterified fatty acids, for maintaining brain PUFA concentrations by comparing brain PUFA concentrations in CD36(-/-) mice to their wild-type littermates. Because CD36(-/-) mice have been reported to have impaired learning ability, the PUFA concentrations in different brain regions (cortex, hippocampus, cerebellum and the remainder of brain) were investigated. At 9 weeks of age, the brain was separated into the four regions and fatty acid concentrations in total and phospholipid classes of these brain regions were analyzed using thin layer and gas chromatography. There were no statistical differences in arachidonic acid or DHA concentrations in the different brain regions between wild-type and CD36(-/-) mice, in total or phospholipid fractions. Concentrations of monounsaturated fatty acids were decreased in several phospholipid fractions in CD36(-/-) mice. These findings suggest that CD36 is not necessary for maintaining brain PUFA concentrations and that other mechanisms must exist.

Higher efficacy of dietary DHA provided as a phospholipid than as a triglyceride for brain DHA accretion in neonatal piglets

“…Despite the well-recognized importance of brain DHA accretion, transport forms of DHA into the brain are not fully understood. Deletion of CD36, an unesterifi ed FA binding protein, in mice does not reduce brain DHA ( 31 ). Similar results were obtained for VLDL receptor-null mice ( 32 ).…”

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

“…The brain obtains DHA directly from the plasma unesterified fatty acid pool, which is maintained in part by hydrolysis of circulating esterified fatty acids synthesized and secreted by the liver, and by adipose triglyceride lipolysis (Demar et al 2005;Gavino and Gavino 1992;Chen et al 2008;Rahman et al 2010a;Song et al 2010;Gao et al 2011). Newly synthesized DHA in liver is secreted into the plasma in triglyceride and phospholipid-rich lipoproteins, which can undergo lipolysis by a DHA-selective endothelial lipase (Chen and Subbaiah 2007).…”

1. The anticonvulsant effects of docosahexaenoic acid in rodents

“…Lipoprotein receptors/transporters do exist in the blood-brain barrier, and these can actively transport FFAs. Knocking out the brain lipoprotein receptors, however, does affect fatty acid concentration in the brain (Song et al, 2010). Transport of FFAs seems to be a passive process.…”

“…Recently, it has become clear that it is the free fatty acids bound to albumin in the blood that are taken up into the brain (Chen et al, 2008a), and that they are taken up by a passive diffusion mechanism and not by active transport . Although the blood-brain barrier does contain lipoprotein transport proteins, mice with these proteins knocked out do not have altered brain fatty acid levels -suggesting that active transport is not the mechanism of lipid uptake into the brain (Chen et al, 2008b;Song et al, 2010).…”