Lipids

, Volume 33, Issue 12, pp 1177–1186

Effect of dietary cholesterol on low density lipoprotein-receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density lipoprotein receptor-related protein mRNA expression in healthy humans

  • Philippe Boucher
  • Michel de Lorgeril
  • Patricia Salen
  • Pierre Crozier
  • Jacques Delaye
  • Jean-Jacques Vallon
  • André Geyssant
  • Robert Dante
Article

DOI: 10.1007/s11745-998-0321-8

Cite this article as:
Boucher, P., de Lorgeril, M., Salen, P. et al. Lipids (1998) 33: 1177. doi:10.1007/s11745-998-0321-8

Abstract

We investigated the possibility that dietary cholesterol downregulates the expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo in healthy humans. We also studied the variations of the LDL receptor-related protein (LRP) gene in the same conditions. Dieters (n=5) were submitted to a 4-d fat restriction (mean cholesterol intake: 6±4 mg/d), followed by a 7-d cholesterol (a mean of 791±150 mg/d) supplementation. Controls (n=3) did not change their diet. During fat restriction, serum total and LDL cholesterol decreased significantly (P<0.05), and LDL receptor and HMG-CoA reductase mRNA copy numbers in mononuclear cells increased by 57 and 147%, respectively (P<0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P<0.05) and LRP mRNA increased by 59% (P<0.005). The changes in LDL receptor and HMG-CoA reductase mRNA abundance were correlated (r=+0.79, P=0.02) during cholesterol reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r=−0.70, P=0.05). Also, 70% of the variability in LRP mRNA (P<0.005) was explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular cholesterol content, the coordinate feedback repression of genes governing the synthesis and uptake of cholesterol, are operating in vivo in humans. However, serum cholesterol did not increase in response to dietary cholesterol, suggesting that these mechanisms may not play as predominant a role as previously believed in the short-term control of serum cholesterol in vivo in humans. A new finding is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may participate in the control of serum cholesterol. Further in vivo studies in humans are warranted to explore the molecular mechanisms of the physiological response to dietary cholesterol in humans.

Abbreviations

CHD

coronary heart disease

GAPDH

glyceraldehyde-3-phosphate dehydrogenase

TIMG-CoA

3-hydroxy-3-methylglutaryl CoA

LDL

low density lipoprotein

LRP

LDL-receptor-related protein

RT-PCR

reverse transcriptase-polymercse chain reaction

VLDL

very low density lipoprotein

Copyright information

© AOCS Press 1998

Authors and Affiliations

  • Philippe Boucher
    • 2
  • Michel de Lorgeril
    • 1
  • Patricia Salen
    • 1
  • Pierre Crozier
    • 2
  • Jacques Delaye
    • 3
  • Jean-Jacques Vallon
    • 2
  • André Geyssant
    • 1
  • Robert Dante
    • 4
  1. 1.Explerations Fonctionnelles Cardiorespiratories et MétaboliquesCHU de saint-Etienne42055 Saint-Etienne Cedex 02France
  2. 2.Laboratoire de Biochimie et Pharmaco-Toxicologie42055 Saint-Etienne Cedex 02France
  3. 3.Hôpital E HerriotHôpital Cardiologique42055 Saint-Etienne Cedex 02France
  4. 4.The Laboratoire de Génétique, CNRS UMR-5641Université Claude BernardLyonFrance