Lipids

, Volume 34, Issue 6, pp 591–598

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

  • Nica M. Borradaile
  • Kenneth K. Carroll
  • Elzbieta M. Kurowska
Article

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.

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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Copyright information

© AOCS Press 1999

Authors and Affiliations

  • Nica M. Borradaile
    • 1
  • Kenneth K. Carroll
    • 1
  • Elzbieta M. Kurowska
    • 1
  1. 1.Department of BiochemistryThe University of Western OntarioLondonCanada

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