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Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple

Nica M Borradaile1, Linda E de Dreu, Lisa J Wilcox

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

The Biochemical Journal
|May 29, 2002
PubMed
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Soya phytoestrogens genistein and daidzein reduce plasma cholesterol by inhibiting hepatocyte apolipoprotein B secretion. These compounds affect cholesterol synthesis, esterification, and low-density lipoprotein receptor expression, offering insights into their hypocholesterolemic effects.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nutritional Science

Background:

  • Soya-derived phytoestrogens, genistein and daidzein, are known to reduce plasma cholesterol in humans and animals.
  • The precise mechanisms underlying these hypocholesterolemic effects remain largely unknown.
  • Understanding these mechanisms is crucial for leveraging dietary interventions for cardiovascular health.

Purpose of the Study:

  • To investigate the effects of genistein and daidzein on cholesterol metabolism in human hepatoma (HepG2) cells.
  • To determine the impact of these isoflavones on apolipoprotein (apo) B secretion and related gene expression.
  • To elucidate the molecular pathways through which genistein and daidzein exert their cholesterol-lowering effects.

Main Methods:

  • Cultured human hepatoma (HepG2) cells were treated with varying concentrations of genistein and daidzein.

Related Experiment Videos

  • Apolipoprotein B (apoB) and apolipoprotein AI (apoAI) secretion were measured.
  • Cellular cholesterol synthesis, esterification, and the activity/expression of key enzymes like HMG-CoA reductase, ACAT, and MTP were assessed.
  • Low-density lipoprotein (LDL) receptor mRNA levels and LDL binding/uptake were analyzed.

    • Main Results:

    • Genistein and daidzein significantly decreased apoB secretion in a dose-dependent manner, without affecting apoAI secretion.
    • Both isoflavones inhibited cellular cholesterol synthesis and cholesterol esterification.
    • Activity and mRNA levels of microsomal triacylglycerol transfer protein (MTP) were reduced by genistein and daidzein.
    • Crucially, LDL-receptor mRNA levels were significantly increased, leading to enhanced LDL uptake.

    Conclusions:

    • Genistein and daidzein inhibit hepatocyte apoB secretion through multiple mechanisms.
    • These mechanisms include the inhibition of cholesterol synthesis and esterification, reduced MTP activity and expression, and increased LDL-receptor expression.
    • These findings provide a molecular basis for the hypocholesterolemic effects of soya isoflavones.