Effect of docosahexaenoic acid on lipoprotein synthesis and secretion by cultured eel hepatocytes.

We investigated effect of docosahexaenoic acid on lipoprotein synthesis and secretion by cultured eel hepatocytes. When eel hepatocytes were incubated with 1 mM docosahexaenoic acid (DHA) at 28 degrees C for 24 h, triacylglycerol (TG), free cholesterol (FC), and cholesteryl ester (CE) syntheses from 14C-acetate increased 9.7-, 1.6-, and 8.5-fold, respectively, and the specific activity of TG was twofold that of control. These results indicate the stimulative effect of DHA on lipid synthesis. However, the radioactivity of the lipoprotein secreted by DHA-treated cells incubated with 14C-acetate and 3H-leucine reduced to 55 and 60%, respectively, compared to that by control cells, but DHA did not affect the incorporation of 3H-leucine into other secreted protein. Furthermore, the amount of the secreted lipoprotein per 24 h by DHA-treated cells also reduced to 17%. These results show that DHA inhibits the secretion of lipoprotein. Intracellular lipids such as TG, PL, and TC increased by 4.8, 1.6, and 1.8 times, respectively, in DHA-treated cells. The remarkable increase in TG in DHA-treated cells seems to be due to the stimulative effect of DHA on TG synthesis and an inhibitory effect of DHA on lipoprotein secretion, since about 70% of the secreted lipoprotein consists of TG. The chemical composition and apoprotein profile of the lipoprotein secreted by DHA-treated and control cells were almost the same. These results suggest that DHA inhibits the assembly or secretion of the lipoprotein in eel hepatocytes.