Administration of n-3 fatty acids in the diets of rats or directly to hepatocyte cultures results in different effects on hepatocellular apoB metabolism and secretion

Hepatocytes derived either from rats fed a diet enriched in n-3 fatty acids or from rats fed a low-fat diet and cultured with an n-3 fatty acid (eicos apentaenoic acid, EPA) in vitro were used to distinguish between the dietar y effects and the direct effects of n-3 fatty acids on hepatocellular apoli poprotein (apo) B metabolism and secretion. ApoB-48 and apoB-100 synthesis, degradation, and secretion as large (d<1.006) and small (d>1.006) particle s were determined after a pulse label with [S-35]methionine. These effects were compared with changes in triacylglycerol (TAG) synthesis and secretion and with changes in de novo fatty acid synthesis (using (H2O)-H-3 incorpor ation) under identical conditions. When n-3 fatty acid was given via the di etary route, apoB-48 very low density lipoprotein (VLDL) secretion was inhi bited, but there was no effect on the secretion of apoB-100 VLDL. There was no effect on the secretion of either apoB-48 or apoB-100 as small, dense p articles (d>1.006). Cellular TAG synthesis was significantly inhibited unde r these conditions, and fatty acid synthesis de novo was inhibited by 80%. By contrast, after direct addition of EPA to hepatocytes from normal rats, the secretion of both, apoB-48 and apoB-100 VLDL was suppressed. The secret ion of apoB-48, but not of apoB-100, as dense particles was also inhibited. However, there was little or no effect on TAG synthesis nor on fatty acid synthesis de novo. In addition, whereas dietary administration of n-3 fatty acid gave rise to decreased net synthesis and degradation of apoB-48, dire ct administration in vitro resulted in increased degradation with no effect on net synthesis. We conclude that the effects of n-3 fatty acids on hepat ic lipid and apoB metabolism differ according to whether they are administe red in vivo, via the dietary route, or in vitro, via direct addition to hep atocyte cultures.