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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500382-JLR200 on November 8, 2005

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Journal of Lipid Research, Vol. 47, 393-403, February 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Saturated fat-induced changes in Sf 60–400 particle composition reduces uptake of LDL by HepG2 cells

Kim G. Jackson1,*, Vatsala Maitin*, David S. Leake{dagger}, Parveen Yaqoob* and Christine M. Williams*

* School of Food Biosciences, University of Reading, Reading, Berkshire, United Kingdom
{dagger} School of Animal and Microbial Sciences, University of Reading, Reading, Berkshire, United Kingdom

Published, JLR Papers in Press, November 8, 2005.

1 To whom correspondence should be addressed. e-mail: k.g.jackson{at}reading.ac.uk

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.

Supplementary key words polyunsaturated fatty acids • monounsaturated fatty acids • apolipoprotein E • apolipoprotein C-III • low density lipoprotein receptor • low density lipoprotein receptor-related protein 1 • real-time reverse transcription polymerase chain reaction • hepatic lipid metabolism • Svedberg flotation rate

Abbreviations: apo, apolipoprotein; FAOX, fatty acyl-coenzyme A oxidase; LRP1, low density lipoprotein receptor-related protein 1; MTP, microsomal triacylglycerol transfer protein; PGC-1ß, peroxisome proliferator-activated receptor {gamma} coactivator-1ß; S1P, site 1 protease; SCAP, sterol-regulatory element binding protein cleavage-activating protein; Sf, Svedberg flotation rate; SFA, saturated fatty acid; SOAT, sterol O-acyltransferase; SREBP, sterol-regulatory element binding protein; TAG, triacylglycerol; TRL, triacylglycerol-rich lipoprotein


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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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