Minor components from dietary oils can modulate the atherogenic response of the TAG-rich lipoproteins (TRL) in which they are transported. In the present study we investigated the influence of TRL isolated from man after the intake of oleic acid-rich oils with different minor component compositions on VLDL secretion by rat primary hepatocytes. TRL were isolated from nine men after the intake of meals enriched with high-oleic sunflower oil (HOSO) or virgin olive oil (VOO) or VOO enriched with minor components (EVO). TRL were incubated with rat primary hepatocytes and the lipid accumulation was analysed in the cells and the secreted VLDL. The expression of genes for proteins related to hepatic lipid metabolism and VLDL production was also measured. Incubation of hepatocytes with TRL derived from HOSO as compared to VOO led to lower intracellular lipid accumulation and VLDL production despite higher mRNA expression for diacylglycerol-acyltransferase, microsomal TAG transfer protein, apoB and PPARα. When TRL derived from EVO were used there were no changes in VLDL secretion. These results suggest that incorporation of minor components from dietary high-oleic oils into TRL modulates the effect of these atherogenic particles on VLDL secretion.

The fatty acid composition of dietary oils can modulate the incorporation of triacylglycerol-rich lipoproteins (TRL) into hepatocytes, thus affecting the atherogenicity of these particles. However, nothing is known about the effect of the unsaponifiable fraction of the oils. In the present study, we evaluated the influence of these components on the uptake of TRL by rat primary hepatocytes. TRL were isolated from human serum after the intake of meals enriched in high-oleic sunflower oil (HOSO), virgin olive oil (VOO) or VOO enriched in its own unsaponifiable fraction (EVO). HOSO and HOSO-TRL differed from VOO and EVO and their corresponding TRL in the composition of triacylglycerol molecular species and of the unsaponifiable fraction. Furthermore, the increase in the unsaponifiable fraction of VOO led to changes in the triacylglycerol molecular species in the EVO-TRL. On incubation with hepatocytes, HOSO-TRL were taken up at a faster rate than VOO-TRL or EVO-TRL. In addition, in comparison to VOO-TRL, HOSO-TRL increased the expression of mRNA for the LDL receptor-related protein receptor, which plays an important role in the internalisation of remnant lipoproteins. EVO-TRL also increased LDL receptor-related protein mRNA expression in comparison with VOO-TRL, but this change was not accompanied by a rise in the uptake rate, suggesting that the unsaponifiable fraction of VOO may inhibit LDL receptor-related protein expression or activity post-transcriptionally. In conclusion, TRL from dietary oils with differing triacylglycerol molecular species and unsaponifiable fraction content are taken up by liver cells at different rates, and this may be important in the atherogenicity of these particles.

This present case report describes two siblings with severe type V hyperlipoproteinaemia, diagnosed very early in life and due to the combination of the common apolipoprotein (Apo) E2 allele and a rare mutant variant of ApoE, ApoE3 (Arg 136 → Ser). Phenotyping of ApoE falsely identified E2/E2 phenotype. The presence of mutated ApoE was suspected on an unusual restriction polymorphism of a Hha 1 restriction site and confirmed by sequence analysis of the cloned polymerase chain reaction fragment of exon 4 and familial segregation study. The severity of the hypertriacylglycerolaemia was modulated by the lipid content of the diet. A low-fat diet enriched in medium-chain triacylglycerol (TAG) decreased but did not normalize plasma TAG levels in both affected patients of the pedigree. A standardized lipid-enriched test meal showed a marked impairment of TAG-rich lipoprotein (TRL) clearance, especially the exogeneous TRL bearing ApoB-48 which still represented 79 % of total TRL 7 h after the fat load. Finally, differences between the male and female siblings with the existence of a consanguine relationship in their parents suggested the involvement of other genetic factors in modulating the severity of phenotypic expression. This observation reinforces the usefulness of genotyping of ApoE for the characterization of genetic hypertriacylglycerolaemia and selection of the appropriate diet and treatment.