Submitted on August 23, 2005
Revised on October 20, 2005
Accepted on November 8, 2005
Saturated fat induced changes in Sf 60-400 particle composition reduces uptake of LDL by HepG2 cells
Kim G Jackson, Vatsala Maitin, David S Leake, Parveen Yaqoob, and Christine M Williams
School of Food Biosciences, The University of Reading, Reading, Berkshire RG6 6AP
Corresponding Author: k.g.jackson{at}reading.ac.uk
The ability of human postprandial triacylglycerol-rich lipoproteins (TRL), isolated following meals enriched in saturated (SFA), n-6 PUFA and monounsaturated (MUFA) fatty acids to inhibit the uptake of 125I-labelled LDL by the LDL-receptor was investigated in HepG2 cells. Addition of TRL resulted in a dose-dependent inhibition of the heparin-releasable binding, cell-associated radioactivity and degradation products of 125I-labelled LDL (P<0.001). SFA-rich Sf 60-400 resulted in significantly greater inhibition of cell-associated radioactivity than PUFA-rich particles (P=0.016) and total uptake of 125I-labelled LDL compared with PUFA- and MUFA-rich particles (P<0.02). Normalisation of the apolipoprotein (apo) E, but not apo C-III content of the TRL, removed the effect of meal fatty acid composition and addition of an anti-apo E antibody reversed the inhibitory effect of TRL on the total uptake of 125I-labelled LDL. Real time RT-PCR, showed that the SFA-rich Sf 60-400 increased the expression of genes involved in hepatic lipid synthesis (P<0.05) and decreased the expression of the LDL-receptor related protein 1 compared with MUFA (P=0.008). In conclusion, these findings suggest an alternative or additional mechanism whereby acute fat ingestion can influence LDL clearance via competitive apo E-dependent effects of TRL on the LDL-receptor.