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Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin

  • Published:
Lipids

Abstract

Our previous studies showed that replacing the drinking water of rabbits fed a casein-containing diet with either orange juice or grapefruit juice reduced serum low density lipoprotein cholesterol and hepatic cholesteryl ester concentrations. To determine whether the changes observed in rabbits were due to flavonoids present in the juices acting directly on the liver’ the effects of hesperetin and naringenin on net apolipoprotein B (apoB) secretion by HepG2 cells were investigated. These flavanones dose-dependently reduced net apoB secretion by up to 81% after a 24 h incubation’ while doses of 60 μg/mL reduced net apoB secretion by 50% after 4 h. Coincubation with the proteasome inhibitor’ MG-132’ did not alter the ability of the flavonoids to reduce net apoB secretion over 4 h’ suggesting that the flavonoid-induced changes in apoB metabolism were not due to a direct increase in proteasomal activity. However’ the flavonoids were unable to reduce net apoB secretion after 4 h in the presence of oleate’ suggesting that these compounds may interfere with the availability of neutral lipids for lipoprotein assembly. Furthermore’ our 14C-acetatelabeling studies showed a 50% reduction in cholesteryl ester synthesis in the presence of either flavonoid’ which could account for the reduction in net apoB secretion caused by incubation with these compounds. These in vitro studies suggest that hesperetin and naringenin may’ in part’ reduce net apoB secretion by HepG2 cells by inhibiting cholesteryl ester synthesis and that these compounds are good candidates for further in vivo studies to determine whether they are responsible for the cholesterol-lowering properties of dietary citrus juices.

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Abbreviations

ACAT:

acyl-CoA acyltransferase

apoB:

apolipoprotein B

BSA:

bovine serum albumin

DMSO:

dimethyl sulfoxide

ELISA:

enzymelinked immunosorbent assay

ER:

endoplasmic reticulum

FBS:

fetal bovine serum

LDL:

low density lipoprotein

MEM:

minimum essential medium

MG-132:

carbobenzoxy-l-leucyl-l-leucyl-l-leucinal

MTP:

microsomal triglyceride transfer protein

MTT:

3-(4’5-dimethylthiazol-2-yl)-2’5-diphenyltetrazolium bromide

TCA:

trichloroacetic acid

VLDL:

very low density lipoprotein

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Authors and Affiliations

  1. Department of Biochemistry, The University of Western Ontario, N6A 5C1, London, Ontario, Canada

    Nica M. Borradaile, Kenneth K. Carroll & Elzbieta M. Kurowska

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  1. Nica M. Borradaile
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  2. Kenneth K. Carroll
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  3. Elzbieta M. Kurowska
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Correspondence to Elzbieta M. Kurowska.

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Borradaile, N.M., Carroll, K.K. & Kurowska, E.M. Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin. Lipids 34, 591–598 (1999). https://doi.org/10.1007/s11745-999-0403-7

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  • DOI: https://doi.org/10.1007/s11745-999-0403-7

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