Figure 1.

Docosahexaenoic acid (DHA) transport through the blood–brain barrier (BBB). Currently known mechanisms of DHA transport are represented in this figure. In blood, albumin can bind non-esterified DHA (NE-DHA), DHA-containing lysophosphatidylcholine (DHA-LysoPC), and DHA-containing phosphatidylcholine (DHA-PC). NE-DHA is released from albumin in the vicinity of endothelial cell membranes and is incorporated into the endothelium by passive diffusion or transportation through fatty acid transport proteins (FATP). DHA-LysoPC is also released from albumin and can be actively transported into the endothelium through the symport major facilitator superfamily domain-containing protein 2A (Mfsd2a). DHA-PC can also be released from albumin and can generate DHA-LysoP C through the action of an endothelial lipase (EL), as shown by Chen and Subbaiah [51]. Lipoproteins are other carriers of NE-DHA and DHA-LysoPC. They can release NE-DHA and DHA-LysoPC through the action of lipoprotein lipases (LPL). Lipoproteins can also bind to their receptors and go through transcystosis. Inside endothelial cells, lipoproteins can be hydrolyzed and can release either NE-DHA or DHA-LysoPC. In the endothelium, NE-DHA is bound to fatty acid binding proteins (FABP) for it to cross the intercellular space to reach brain cells. NE-DHA can either diffuse passively through the endothelial-brain barrier or be transported through FATP.