Essential polyunsaturated fatty acids and the barrier to the brain - The components of a model for transport

Several areas of research have contributed to the establishment of a paradi gm that meets the requirements for the selective uptake of essential polyun saturated fatty acids (EPUFA) into brain. First, discrete studies have demo nstrated that cholesterol and the nonessential fatty acids, (palmitic, olei c, stearic) do not enter the brain parenchyma. These studies demonstrated t hat the 18 carbon-monocarboxylic fatty acids, linoleic acid with two cis-do uble bonds entered brain, whereas oleic acid, with one cis-double bond, did not enter brain. It was concluded the entry of essential fatty acids into brain is accomplished in a highly selective and discrete manner. Further, t he typical blood-borne lipoproteins do not traverse the endothelial cells o f the capillary network and enter into the brain, otherwise cholesterol, pa lmitic, oleic, and stearic acids from blood would be located within brain. Second, several investigators have shown that the endothelial cells of the capillary network contain lipoprotein receptors, yet one conclusion is that the brain does not utilize low-density lipoprotein (LDL)cholesterol. Third , recently, the existence and function of a significant number of distincti ve trans-membrane monocarboxylic acid transporters, (MCTs) and fatty acid t ransport proteins (FATPs) have been described. No transporters have been de scribed to date with the specificity necessary to transfer only EPUFA into brain. A blueprint with the minimal elements for delivery and selectivity i s proposed. Lipoproteins enter the endothelial cells because the lipoprotei n receptors are positioned on their luminal membrane. Essential fatty acid transporter(s) are positioned on the abluminal membrane of these endothelia l cells to allow for the entry of EPUFA into brain. Within the endothelial cell there is opportunity for lipid management and transformation such that EPUFAs are selectively culled for delivery to the essential fatty acid tra nsporter(s), which facilitates their transfer into brain.