DIFFERENTIAL-EFFECTS OF EICOSAPENTAENOIC ACID ON GLYCEROLIPID AND APOLIPOPROTEIN-B METABOLISM IN PRIMARY HUMAN HEPATOCYTES COMPARED TO HEPG2 CELLS AND PRIMARY RAT HEPATOCYTES

We compared the effects of eicosapentaenoic acid (EPA) and oleic acid (OA) on glycerolipid and apolipoprotein B (apoB) metabolism in primary human hepatocytes, HepG2 cells and primary rat hepatocytes. Cells were incubated for 1 to 5 h with 0.25 mM bovine serum albumin in the absence (control) or presence of 1 mM of EPA or OA. Synthesis and secretion of [H-3]glycerolipid were determined after 1 h incubation with [H-3]glycerol. Cellular and medium apoB abundance was semi-quantitatively estimated in human cells by Western blotting. The following observations were made. (1) Compared to control, OA induced a 7-fold increase in [H-3]triacylglycerol (TG) synthesis in human hepatocytes and a 4-fold increase in rat hepatocytes and HepG2 cells. EPA enhanced [H-3]TG synthesis about 2-fold in all three cell types although it stimulated [H-3]diacylglycerol (DG) synthesis to an extent (i.e., 2.5- to 5-fold) similar to OA. (2) In contrast to OA, which stimulated VLDL-associated [H-3]TG secretion 2.5- to 3-fold in the three cell types relative to control, EPA did not alter [H-3]TG secretion in HepG2 and rat hepatocytes and suppressed [H-3]TG secretion by 75% in primary human hepatocytes. (3) In primary human hepatocytes, both OA and EPA did not alter cellular apoB abundance but EPA decreased apoB secretion by 44% as compared to control. In contrast, both EPA and OA increased cellular and medium apoB abundance 2- to 2.5-fold in HepG2 cells, although medium apoB tended to be lower in EPA-treated cells. (4) EPA had no effect on the [H-3]phosphatidylcholine (PC) synthesis in rat hepatocytes, but decreased [H-3]PC synthesis by 30% in human hepatocytes and HepG2 cells. This study shows that, in primary human hepatocytes, EPA decreases TG secretion below control Values by influencing VLDL particle assembly and/or secretion. There are both qualitative and quantitative differences in the effects of EPA and OA on the glycerolipid and apoB metabolism between primary human hepatocytes and both HepG2 and primary rat hepatocytes, the two most commonly used model systems to investigate hepatic lipid metabolism in vitro.