Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain

Abstract

Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.

Threshold changes in rat brain docosahexaenoic acid incorporation and concentration following graded reductions in dietary alpha-linolenic acid

“…In these studies, however, brain DHA uptake was assessed by quantifying the percent 14 C of injected radioactivity, and without correcting for the fractional uptake of 14 C-DHA from the plasma, since 14 C-DHA was not infused to steady-state levels. A recent study that quantitatively compared the incorporation of free and esterified DHA into the brain by infusing both to steady-state levels, reported that unesterified DHA is the main source of brain DHA [43]. …”

[P3–317]: DHA BRAIN UPTAKE AND APOE4 STATUS: A PET STUDY WITH [1‐11C]‐DHA

“…APOE genotype may influence the metabolism of DHA in the brain or its delivery to the brain, although brain DHA delivery may not directly depend on peripheral lipoproteins [18]. In humans, whole body DHA halflife was lower in APOE4 carriers than in noncarriers, which was attributed to greater liver oxidation of DHA [19].…”

DHA brain uptake and APOE4 status: a PET study with [1-11C]-DHA

“…APOE genotype may influence the metabolism of DHA in the brain or its delivery to the brain, although brain DHA delivery may not directly depend on peripheral lipoproteins [18]. In humans, whole body DHA half-life was lower in APOE4 carriers than in noncarriers, which was attributed to greater liver oxidation of DHA [19].…”