Role of liver and plasma lipoproteins in selective transport of n-3 fatty acids to tissues: A comparative study of C-14-DHA and H-3-oleic acid tracers

We conducted a study aimed at a direct comparison of the plasma dynamics and uptake of docosahexaenoic (DHA) and oleic (OA) fatty acids by various organs. C-14-DHA and H-3-OA were intravenously co-injected into mice. At 5 min after injection, more than 40% of the C-14-DHA, but less than 20% of the H-3-OA, labels was associated with the liver. Heart uptake of C-14-DHA was three to four times greater compared to the H-3-OA label. Brain incorporation of C-14-DHA slowly rose to 0.7% at 24 h, but it remained at the 1-1.5% level for 3H-OA. Total 14 C activity in plasma reached 2% of the injected dose at 20 min and leveled off at 0.5% after 1.5 h. Fifteen percent of C-14-DHA plasma activity at 30 min was associated with non-esterified fatty acids, whereas about 85% was recovered in triglycerides in very low-density lipoprotem (VLDL) and LDL fractions. Only 30% of H-3-OA derived activity was found in the VLDL fraction at 30 min. All H-3 activity in plasma at later time points was in catabolite fractions. These findings demonstrate that liver plays an important role in the initial selectivity for DHA. It is likely that DHA is specifically taken up by liver, esterified, loaded into lipoproteins, and then delivered to brain, heart, and other target tissues.