Key result
Dietary n-3 fatty acids reduce hepatocyte de novo fatty acid synthesis and VLDL secretion by ~80%.
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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 (eicosapentaenoic acid, EPA) in vitro were used to distinguish between the dietary effects and the direct effects of n-3 fatty acids on hepatocellular apolipoprotein (apo) B metabolism and secretion. ApoB-48 and apoB-100 synthesis, degradation, and secretion as large (d<1.006) and small (d>1.006) particles were determined after a pulse label with [35S]methionine. These effects were compared with changes in triacylglycerol (TAG) synthesis and secretion and with changes in de novo fatty acid synthesis (using 3H2O incorporation) under identical conditions. When n-3 fatty acid was given via the dietary route, apoB-48 very low density lipoprotein (VLDL) secretion was inhibited, 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 particles (d>1.006). Cellular TAG synthesis was significantly inhibited under 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 secretion 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, direct administration in vitro resulted in increased degradation with no effect on net synthesis. We conclude that the effects of n-3 fatty acids on hepatic lipid and apoB metabolism differ according to whether they are administered in vivo, via the dietary route, or in vitro, via direct addition to hepatocyte cultures.
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Brown et al. (1999) studied Hepatocellular apolipoprotein B and lipid metabolism. Dietary n-3 fatty acids vs. in vitro eicosapentaenoic acid (EPA) vs. Low-fat diet / untreated normal rat hepatocytes was evaluated on Hepatocellular apoB-48 and apoB-100 synthesis, degradation, and secretion, alongside triacylglycerol and de novo fatty acid synthesis. Dietary n-3 fatty acids inhibited rat hepatocyte apoB-48 VLDL secretion and de novo fatty acid synthesis by 80%, whereas in vitro EPA suppressed both apoB-48 and apoB-100 VLDL secretion.
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