Incorporation of docosahexaenoic acid into nerve membrane phospholipids: bridging the gap between animals and cultured cells

Background: Functional maturation of nervous tissues depends on membrane accretion of docosahexaenoic acid (DHA). Animal studies have shown that incorporation of dietary DHA into membrane phospholipids is dose dependent. The molecular effects of DHA are commonly studied in cultured cells, but questions remain about the physiologic connection between animal and cell models. Objective: We developed a linear model for comparing the responses of rat nervous tissues to dietary DHA with the responses of human cell lines to DHA in medium. Design: Rats were rendered chronically deficient in n-3 fatty acids by being reared on a peanut oil diet. DHA status was replenished in the F2 generation by using increasing supplements of a microalgal oil. Human retinoblastoma and neuroblastoma cells were dosed with unesterified DHA. DHA accumulation into phospholipids was defined by the plateau of the dose-response curve (DHAmax) and by the supplement required to produce one-half the DHAmax (DHA50). Results: The DHAmax values for 4 brain regions and 2 neuroblastoma lines were similar, and the value for the retinoblastoma line was similar to the retinal value. Expressing the DHA input as μmol/10 g diet and as μmol/L medium resulted in similar values for the ratio of DHAmax to DHA50 in the 4 brain regions and the 3 cell lines. The DHAmax-DHA50 ratios in the ethanolamine phosphoglyceride and phosphatidylcholine fractions in retinal phospholipids were 6 and 10 times, respectively, those in the brain and cultured cells. Conclusions: The dose-dependent responses of cells and the brain to DHA supplements can be compared by using DHAmax-DHA50 ratios. We propose a counting frame that allows the comparison of the dose responses of the brain and cells to exogenous DHA.