BIOMAT Database Logo BIOMAT Database Logo

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. 1998

P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
The Laboratoire de Biochimie et Pharmaco-Toxicologie, CNRS UMR-5641, Université Claude Bernard, Lyon, France.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011971 Receptors, Immunologic Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere. Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D002791 Cholesterol, Dietary Cholesterol present in food, especially in animal products. Dietary Cholesterol
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006903 Hydroxymethylglutaryl CoA Reductases Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID. HMG CoA Reductases,3-Hydroxy-3-methylglutaryl CoA Reductase,HMG CoA Reductase,Hydroxymethylglutaryl CoA Reductase,3 Hydroxy 3 methylglutaryl CoA Reductase,CoA Reductase, 3-Hydroxy-3-methylglutaryl,Reductase, 3-Hydroxy-3-methylglutaryl CoA
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

Related Publications

P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Effect of dietary cholesterol and cholestyramine on developmental pattern of 3-hydroxy-3-methylglutaryl-CoA reductase.
January 1985, Annals of nutrition & metabolism,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase unmask transcriptional regulation of hepatic low-density lipoprotein receptor gene expression by dietary cholesterol.
August 1997, Archives of biochemistry and biophysics,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Oxysterol regulators of 3-hydroxy-3-methylglutaryl-CoA reductase in liver. Effect of dietary cholesterol.
April 1989, The Journal of biological chemistry,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Co-ordinate regulation of low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase and synthase gene expression in HepG2 cells.
June 1989, The Biochemical journal,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol.
September 2005, The American journal of cardiology,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity, cholesterol esterification and the expression of low-density lipoprotein receptors in cultured monocyte-derived macrophages.
February 1983, The Biochemical journal,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein.
October 1995, The Biochemical journal,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
3-Hydroxy-3-methylglutaryl-CoA reductase.
January 2000, Methods in enzymology,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR).
June 2013, The Journal of biological chemistry,
P Boucher, and M de Lorgeril, and P Salen, and P Crozier, and J Delaye, and J J Vallon, and A Geyssant, and R Dante
Differential regulation of the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, synthase, and low density lipoprotein receptor genes.
August 1992, Journal of lipid research,
Copied contents to your clipboard!