Saturated fat-induced changes in Sf 60-400 particle composition reduces uptake of LDL by HepG2 cells.
The ability of human postprandial triacylglycerol-rich lipoproteins (TRLs), isolated after meals enriched in saturated fatty acids (SFAs), n-6 PUFAs, and MUFAs, to inhibit the uptake of 125I-labeled LDL by the LDL receptor was investigated in HepG2 cells. Addition of TRLs resulted in a dose-dependent inhibition of heparin-releasable binding, cell-associated radioactivity, and degradation products of 125I-labeled LDL (P < 0.001). SFA-rich Svedberg flotation rate (Sf) 60-400 resulted in significantly greater inhibition of cell-associated radioactivity than PUFA-rich particles (P = 0.016) and total uptake of 125I-labeled LDL compared with PUFA- and MUFA-rich particles (P < 0.02). Normalization of the apolipoprotein (apo)E but not apoC-III content of the TRLs removed the effect of meal fatty acid composition, and addition of an anti-apoE antibody reversed the inhibitory effect of TRLs on the total uptake of 125I-labeled 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 MUFAs (P = 0.008). In conclusion, these findings suggest an alternative or additional mechanism whereby acute fat ingestion can influence LDL clearance via competitive apoE-dependent effects of TRL on the LDL receptor.
Jackson
Kim G
KG
School of Food Biosciences, University of Reading, Reading, Berkshire, United Kingdom. k.g.jackson@reading.ac.uk
Maitin
Vatsala
V
Leake
David S
DS
Yaqoob
Parveen
P
Williams
Christine M
CM
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000032:analysis / Q000235:genetics; D001056:Apolipoproteins C / Q000032:analysis; D001057:Apolipoproteins E / Q000032:analysis / Q000276:immunology; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000032:analysis; D002914:Chylomicrons / Q000737:chemistry / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000235:genetics; D005227:Fatty Acids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D043484:Proprotein Convertases / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics; D002785:Sterol O-Acyltransferase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014280:Triglycerides / Q000032:analysis
D000911:Antibodies, Monoclonal; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D002914:Chylomicrons; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008565:Membrane Proteins; D011973:Receptors, LDL; C497387:SREBF1 protein, human; C102196:SREBP cleavage-activating protein; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase; D064429:Fatty Acid Synthases; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1