Diets containing the soya-derived phytoestrogens, genistein and daidzein, decrease plasma cholesterol in humans and experimental animals. The mechanisms responsible for the hypocholesterolaemic effects of these isoflavones are unknown. The present study was conducted to determine if genistein and daidzein regulate hepatocyte cholesterol metabolism and apolipoprotein (apo) B secretion in cultured human hepatoma (HepG2) cells. ApoB secretion was decreased dose-dependently by up to 63% and 71% by genistein and daidzein (100μM; P<0.0001) respectively. In contrast, no effect on apoAI secretion was observed. Cellular cholesterol synthesis was inhibited 41% by genistein (100μM; P<0.005) and 18% by daidzein (100μM; P<0.05), which was associated with significant increases in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA. Cellular cholesterol esterification was decreased 56% by genistein (100μM; P<0.04) and 29% by daidzein (100μM; P<0.04); however, mRNA levels for acyl-CoA:cholesterol acyltransferase (ACAT) 1 and ACAT2 were unaffected. At 100μM, both isoflavones equally inhibited the activities of both forms of ACAT in cells transfected with either ACAT1 or ACAT2. Genistein (100μM) and daidzein (100μM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. Both isoflavones increased low-density lipoprotein (LDL)-receptor mRNA levels by 3- to 6-fold (100μM; P<0.03) and significantly increased the binding, uptake and degradation of 125I-labelled LDL, suggesting that enhanced reuptake of newly secreted apoB-containing lipoproteins contributed to the net decrease in apoB secretion. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition of cholesterol synthesis and esterification, inhibition of MTP activity and expression and increased expression of the LDL-receptor.
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September 2002
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Research Article|
September 01 2002
Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms
Nica M. BORRADAILE;
Nica M. BORRADAILE
1
∗Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5C1
†The John P. Robarts Research Institute, 100 Perth Drive, London, ON, Canada N6A 5K8,
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Linda E. de DREU;
Linda E. de DREU
1
†The John P. Robarts Research Institute, 100 Perth Drive, London, ON, Canada N6A 5K8,
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Lisa J. WILCOX;
Lisa J. WILCOX
2
∗Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5C1
†The John P. Robarts Research Institute, 100 Perth Drive, London, ON, Canada N6A 5K8,
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Jane Y. EDWARDS;
Jane Y. EDWARDS
†The John P. Robarts Research Institute, 100 Perth Drive, London, ON, Canada N6A 5K8,
‡Department of Medicine, University of Western Ontario, London, ON, Canada N6A 5C1
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Murray W HUFF
Murray W HUFF
3
∗Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5C1
†The John P. Robarts Research Institute, 100 Perth Drive, London, ON, Canada N6A 5K8,
‡Department of Medicine, University of Western Ontario, London, ON, Canada N6A 5C1
3To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
January 09 2002
Revision Received:
April 18 2002
Accepted:
May 28 2002
Accepted Manuscript online:
May 28 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (2): 531–539.
Article history
Received:
January 09 2002
Revision Received:
April 18 2002
Accepted:
May 28 2002
Accepted Manuscript online:
May 28 2002
Citation
Nica M. BORRADAILE, Linda E. de DREU, Lisa J. WILCOX, Jane Y. EDWARDS, Murray W HUFF; Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms. Biochem J 1 September 2002; 366 (2): 531–539. doi: https://doi.org/10.1042/bj20020046
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