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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 S_f 60–400 particle composition reduces uptake of LDL by HepG2 cells

Kim G. Jackson^1,*, Vatsala Maitin^*, David S. Leake, Parveen Yaqoob^* and Christine M. Williams^*

^* School of Food Biosciences, University of Reading, Reading, Berkshire, United Kingdom
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 (S_f) 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 S_f 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 coactivator-1ß; S1P, site 1 protease; SCAP, sterol-regulatory element binding protein cleavage-activating protein; S_f, 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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