Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Molecular Insights into the Mechanisms Underlying the Cholesterol- Lowering Effects of Phytosterols

Author(s): Lídia Cedó, Marta Farràs, Miriam Lee-Rueckert and Joan Carles Escolà-Gil*

Volume 26, Issue 37, 2019

Page: [6704 - 6723] Pages: 20

DOI: 10.2174/0929867326666190822154701

Price: $65

Abstract

Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma Low-Density Lipoprotein-Cholesterol (LDL-C) levels when given 2 g/day. Since this dose has not been reported to cause health-related side effects in long-term human studies, food products containing these plant compounds are used as potential therapeutic dietary options to reduce LDL-C and cardiovascular disease risk. Several mechanisms have been proposed to explain the cholesterol-lowering action of phytosterols. They may compete with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption. Recent evidence indicates that phytosterols may also regulate other pathways. Impaired intestinal cholesterol absorption is usually associated with reduced cholesterol transport to the liver, which may reduce the incorporation of cholesterol into Very-Low- Density Lipoprotein (VLDL) particles, thereby lowering the rate of VLDL assembly and secretion. Impaired liver VLDL production may reduce the rate of LDL production. On the other hand, significant evidence supports a role for plant sterols in the Transintestinal Cholesterol Excretion (TICE) pathway, although the exact mechanisms by which they promote the flow of cholesterol from the blood to enterocytes and the intestinal lumen remains unknown. Dietary phytosterols may also alter the conversion of bile acids into secondary bile acids, and may lower the bile acid hydrophobic/hydrophilic ratio, thereby reducing intestinal cholesterol absorption. This article reviews the progress to date in research on the molecular mechanisms underlying the cholesterol-lowering effects of phytosterols.

Keywords: Bile acids, cholesterol absorption, intestine, low-density lipoproteins, liver, phytosterols, TICE.

« Previous Next »
[1]
Ikonen, E. Cellular cholesterol trafficking and compartmentalization. Nat. Rev. Mol. Cell Biol., 2008, 9(2), 125-138.
[http://dx.doi.org/10.1038/nrm2336] [PMID: 18216769]
[2]
Ference, B.A.; Ginsberg, H.N.; Graham, I.; Ray, K.K.; Packard, C.J.; Bruckert, E.; Hegele, R.A.; Krauss, R.M.; Raal, F.J.; Schunkert, H.; Watts, G.F.; Borén, J.; Fazio, S.; Horton, J.D.; Masana, L.; Nicholls, S.J.; Nordestgaard, B.G.; van de Sluis, B.; Taskinen, M.R.; Tokgözoglu, L.; Landmesser, U.; Laufs, U.; Wiklund, O.; Stock, J.K.; Chapman, M.J.; Catapano, A.L. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J., 2017, 38(32), 2459-2472.
[http://dx.doi.org/10.1093/eurheartj/ehx144] [PMID: 28444290]
[3]
Lloyd-Jones, D.M.; Morris, P.B.; Ballantyne, C.M.; Birtcher, K.K.; Daly, D.D., Jr; DePalma, S.M.; Minissian, M.B.; Orringer, C.E.; Smith, S.C. Jr. 2017 focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American college of cardiology task force on expert consensus decision pathways. J. Am. Coll. Cardiol., 2017, 70(14), 1785-1822.
[http://dx.doi.org/10.1016/j.jacc.2017.07.745] [PMID: 28886926]
[4]
Cannon, C.P.; Blazing, M.A.; Giugliano, R.P.; McCagg, A.; White, J.A.; Theroux, P.; Darius, H.; Lewis, B.S.; Ophuis, T.O.; Jukema, J.W.; De Ferrari, G.M.; Ruzyllo, W.; De Lucca, P. Im, K.; Bohula, E.A.; Reist, C.; Wiviott, S.D.; Tershakovec, A.M.; Musliner, T.A.; Braunwald, E.; Califf, R.M.; IMPROVE-IT investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med., 2015, 372(25), 2387-2397.
[http://dx.doi.org/10.1056/NEJMoa1410489] [PMID: 26039521]
[5]
Klingberg, S.; Andersson, H.; Mulligan, A.; Bhaniani, A.; Welch, A.; Bingham, S.; Khaw, K.T.; Andersson, S.; Ellegård, L. Food sources of plant sterols in the EPIC Norfolk population. Eur. J. Clin. Nutr., 2008, 62(6), 695-703.
[http://dx.doi.org/10.1038/sj.ejcn.1602765] [PMID: 17440516]
[6]
Gylling, H.; Plat, J.; Turley, S.; Ginsberg, H.N.; Ellegård, L.; Jessup, W.; Jones, P.J.; Lütjohann, D.; Maerz, W.; Masana, L.; Silbernagel, G.; Staels, B.; Borén, J.; Catapano, A.L.; De Backer, G.; Deanfield, J.; Descamps, O.S.; Kovanen, P.T.; Riccardi, G.; Tokgözoglu, L.; Chapman, M.J. European Atherosclerosis Society Consensus Panel on Phytosterols. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis, 2014, 232(2), 346-360.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.043] [PMID: 24468148]
[7]
Racette, S.B.; Lin, X.; Lefevre, M.; Spearie, C.A.; Most, M.M.; Ma, L.; Ostlund, R.E. Jr. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study. Am. J. Clin. Nutr., 2010, 91(1), 32-38.
[http://dx.doi.org/10.3945/ajcn.2009.28070] [PMID: 19889819]
[8]
Blair, S.N.; Capuzzi, D.M.; Gottlieb, S.O.; Nguyen, T.; Morgan, J.M.; Cater, N.B. Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am. J. Cardiol., 2000, 86(1), 46-52.
[http://dx.doi.org/10.1016/S0002-9149(00)00976-0] [PMID: 10867091]
[9]
Castro Cabezas, M.; de Vries, J.H.; Van Oostrom, A.J.; Iestra, J.; van Staveren, W.A. Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in patients treated with statins. J. Am. Diet. Assoc., 2006, 106(10), 1564-1569.
[http://dx.doi.org/10.1016/j.jada.2006.07.009] [PMID: 17000189]
[10]
Ostlund, R.E., Jr; McGill, J.B.; Zeng, C.M.; Covey, D.F.; Stearns, J.; Stenson, W.F.; Spilburg, C.A. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am. J. Physiol. Endocrinol. Metab., 2002, 282(4), E911-E916.
[http://dx.doi.org/10.1152/ajpendo.00328.2001] [PMID: 11882512]
[11]
Bosner, M.S.; Lange, L.G.; Stenson, W.F.; Ostlund, R.E. Jr. Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry. J. Lipid Res., 1999, 40(2), 302-308.
[PMID: 9925660]
[12]
Hendriks, H.F.; Brink, E.J.; Meijer, G.W.; Princen, H.M.; Ntanios, F.Y. Safety of long-term consumption of plant sterol esters-enriched spread. Eur. J. Clin. Nutr., 2003, 57(5), 681-692.
[http://dx.doi.org/10.1038/sj.ejcn.1601598] [PMID: 12771969]
[13]
Fransen, H.P.; de Jong, N.; Wolfs, M.; Verhagen, H.; Verschuren, W.M.; Lütjohann, D.; von Bergmann, K.; Plat, J.; Mensink, R.P. Customary use of plant sterol and plant stanol enriched margarine is associated with changes in serum plant sterol and stanol concentrations in humans. J. Nutr., 2007, 137(5), 1301-1306.
[http://dx.doi.org/10.1093/jn/137.5.1301] [PMID: 17449596]
[14]
Brinton, E.A.; Hopkins, P.N.; Hegele, R.A.; Geller, A.S.; Polisecki, E.Y.; Diffenderfer, M.R.; Schaefer, E.J. The association between hypercholesterolemia and sitosterolemia, and report of a sitosterolemia kindred. J. Clin. Lipidol., 2018, 12(1), 152-161.
[http://dx.doi.org/10.1016/j.jacl.2017.10.013] [PMID: 29169939]
[15]
Gylling, H.; Simonen, P. Phytosterols, phytostanols, and lipoprotein metabolism. Nutrients, 2015, 7(9), 7965-7977.
[http://dx.doi.org/10.3390/nu7095374] [PMID: 26393644]
[16]
Hovenkamp, E.; Demonty, I.; Plat, J.; Lütjohann, D.; Mensink, R.P.; Trautwein, E.A. Biological effects of oxidized phytosterols: a review of the current knowledge. Prog. Lipid Res., 2008, 47(1), 37-49.
[http://dx.doi.org/10.1016/j.plipres.2007.10.001] [PMID: 18022398]
[17]
Grandgirard, A.; Martine, L.; Joffre, C.; Juaneda, P.; Berdeaux, O. Gas chromatographic separation and mass spectrometric identification of mixtures of oxyphytosterol and oxycholesterol derivatives application to a phytosterol-enriched food. J. Chromatogr. A, 2004, 1040(2), 239-250.
[http://dx.doi.org/10.1016/j.chroma.2004.04.008] [PMID: 15230531]
[18]
Grandgirard, A.; Martine, L.; Demaison, L.; Cordelet, C.; Joffre, C.; Berdeaux, O.; Semon, E. Oxyphytosterols are present in plasma of healthy human subjects. Br. J. Nutr., 2004, 91(1), 101-106.
[http://dx.doi.org/10.1079/BJN20031025] [PMID: 14748942]
[19]
Baumgartner, S.; Mensink, R.P.; Husche, C.; Lütjohann, D.; Plat, J. Effects of plant sterol- or stanol-enriched margarine on fasting plasma oxyphytosterol concentrations in healthy subjects. Atherosclerosis, 2013, 227(2), 414-419.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.01.012] [PMID: 23375753]
[20]
Baumgartner, S.; Mensink, R.P.; den Hartog, G.; Bast, A.; Bekers, O.; Husche, C.; Lütjohann, D.; Plat, J. Oxyphytosterol formation in humans: identification of high vs. low oxidizers. Biochem. Pharmacol., 2013, 86(1), 19-25.
[http://dx.doi.org/10.1016/j.bcp.2013.02.035] [PMID: 23500537]
[21]
Baumgartner, S.; Mensink, R. P.; Konings, M.; Schott, H. F.; Friedrichs, S.; Husche, C.; Lutjohann, D.; Plat, J. Postprandial plasma oxyphytosterol concentrations after consumption of plant sterol or stanol enriched mixed meals in healthy subjects. Steroids, 2015, 99(Pt B), 281-286.
[http://dx.doi.org/10.1016/j.steroids.2015.01.017] [PMID: 25656784]
[22]
Kidambi, S.; Patel, S.B. Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis. J. Clin. Pathol., 2008, 61(5), 588-594.
[http://dx.doi.org/10.1136/jcp.2007.049775] [PMID: 18441155]
[23]
Escolà-Gil, J.C.; Quesada, H.; Julve, J.; Martín-Campos, J.M.; Cedó, L.; Blanco-Vaca, F. Sitosterolemia: diagnosis, investigation, and management. Curr. Atheroscler. Rep., 2014, 16(7), 424.
[http://dx.doi.org/10.1007/s11883-014-0424-2] [PMID: 24821603]
[24]
Dempsey, M.E.; Farquhar, J.W.; Smith, R.E. The effect of beta sitosterol on the serum lipids of young men with arteriosclerotic heart disease. Circulation, 1956, 14(1), 77-82.
[http://dx.doi.org/10.1161/01.CIR.14.1.77] [PMID: 13356460]
[25]
Miettinen, T.A.; Puska, P.; Gylling, H.; Vanhanen, H.; Vartiainen, E. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N. Engl. J. Med., 1995, 333(20), 1308-1312.
[http://dx.doi.org/10.1056/NEJM199511163332002] [PMID: 7566021]
[26]
Ras, R.T.; Geleijnse, J.M.; Trautwein, E.A. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br. J. Nutr., 2014, 112(2), 214-219.
[http://dx.doi.org/10.1017/S0007114514000750] [PMID: 24780090]
[27]
Musa-Veloso, K.; Poon, T.H.; Elliot, J.A.; Chung, C. A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: results of a meta-analysis of randomized, placebo-controlled trials. Prostaglandins Leukot. Essent. Fatty Acids, 2011, 85(1), 9-28.
[http://dx.doi.org/10.1016/j.plefa.2011.02.001] [PMID: 21345662]
[28]
Demonty, I.; Ras, R.T.; van der Knaap, H.C.; Duchateau, G.S.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J. Nutr., 2009, 139(2), 271-284.
[http://dx.doi.org/10.3945/jn.108.095125] [PMID: 19091798]
[29]
Jones, P.J.; Raeini-Sarjaz, M.; Ntanios, F.Y.; Vanstone, C.A.; Feng, J.Y.; Parsons, W.E. Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J. Lipid Res., 2000, 41(5), 697-705.
[PMID: 10787430]
[30]
Ferguson, J.J.; Stojanovski, E.; MacDonald-Wicks, L.; Garg, M.L. Fat type in phytosterol products influence their cholesterol-lowering potential: A systematic review and meta-analysis of RCTs. Prog. Lipid Res., 2016, 64, 16-29.
[http://dx.doi.org/10.1016/j.plipres.2016.08.002] [PMID: 27497855]
[31]
De Smet, E.; Mensink, R.P.; Plat, J. Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present. Mol. Nutr. Food Res., 2012, 56(7), 1058-1072.
[http://dx.doi.org/10.1002/mnfr.201100722] [PMID: 22623436]
[32]
Liang, Y.T.; Wong, W.T.; Guan, L.; Tian, X.Y.; Ma, K.Y.; Huang, Y.; Chen, Z.Y. Effect of phytosterols and their oxidation products on lipoprotein profiles and vascular function in hamster fed a high cholesterol diet. Atherosclerosis, 2011, 219(1), 124-133.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.06.004] [PMID: 21719014]
[33]
Plat, J.; Theuwissen, E.; Husche, C.; Lütjohann, D.; Gijbels, M.J.; Jeurissen, M.; Shiri-Sverdlov, R.; van der Made, I.; Mensink, R.P. Oxidised plant sterols as well as oxycholesterol increase the proportion of severe atherosclerotic lesions in female LDL receptor+/- mice. Br. J. Nutr., 2014, 111(1), 64-70.
[http://dx.doi.org/10.1017/S0007114513002018] [PMID: 23773414]
[34]
Tomoyori, H.; Kawata, Y.; Higuchi, T.; Ichi, I.; Sato, H.; Sato, M.; Ikeda, I.; Imaizumi, K. Phytosterol oxidation products are absorbed in the intestinal lymphatics in rats but do not accelerate atherosclerosis in apolipoprotein E-deficient mice. J. Nutr., 2004, 134(7), 1690-1696.
[http://dx.doi.org/10.1093/jn/134.7.1690] [PMID: 15226455]
[35]
Fumeron, F.; Bard, J.M.; Lecerf, J.M. Interindividual variability in the cholesterol-lowering effect of supplementation with plant sterols or stanols. Nutr. Rev., 2017, 75(2), 134-145.
[http://dx.doi.org/10.1093/nutrit/nuw059] [PMID: 28158760]
[36]
Jones, P.J. Inter-individual variability in response to plant sterol and stanol consumption. J. AOAC Int., 2015, 98(3), 724-728.
[http://dx.doi.org/10.5740/jaoacint.SGEJones] [PMID: 25942064]
[37]
Wang, D.Q. Regulation of intestinal cholesterol absorption. Annu. Rev. Physiol., 2007, 69, 221-248.
[http://dx.doi.org/10.1146/annurev.physiol.69.031905.160725] [PMID: 17002594]
[38]
Lee, S.D.; Gershkovich, P.; Darlington, J.W.; Wasan, K.M. Inhibition of cholesterol absorption: targeting the intestine. Pharm. Res., 2012, 29(12), 3235-3250.
[http://dx.doi.org/10.1007/s11095-012-0858-6] [PMID: 22923351]
[39]
Lee-Rueckert, M.; Blanco-Vaca, F.; Kovanen, P.T.; Escola-Gil, J.C. The role of the gut in reverse cholesterol transport--focus on the enterocyte. Prog. Lipid Res., 2013, 52(3), 317-328.
[http://dx.doi.org/10.1016/j.plipres.2013.04.003] [PMID: 23608233]
[40]
Thurnhofer, H.; Hauser, H. Uptake of cholesterol by small intestinal brush border membrane is protein-mediated. Biochemistry, 1990, 29(8), 2142-2148.
[http://dx.doi.org/10.1021/bi00460a026] [PMID: 2328246]
[41]
Abumrad, N.A.; Davidson, N.O. Role of the gut in lipid homeostasis. Physiol. Rev., 2012, 92(3), 1061-1085.
[http://dx.doi.org/10.1152/physrev.00019.2011] [PMID: 22811425]
[42]
Altmann, S.W.; Davis, H.R., Jr; Zhu, L.J.; Yao, X.; Hoos, L.M.; Tetzloff, G.; Iyer, S.P.; Maguire, M.; Golovko, A.; Zeng, M.; Wang, L.; Murgolo, N.; Graziano, M.P. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science, 2004, 303(5661), 1201-1204.
[http://dx.doi.org/10.1126/science.1093131] [PMID: 14976318]
[43]
Davis, H.R., Jr; Zhu, L.J.; Hoos, L.M.; Tetzloff, G.; Maguire, M.; Liu, J.; Yao, X.; Iyer, S.P.; Lam, M.H.; Lund, E.G.; Detmers, P.A.; Graziano, M.P.; Altmann, S.W. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J. Biol. Chem., 2004, 279(32), 33586-33592.
[http://dx.doi.org/10.1074/jbc.M405817200] [PMID: 15173162]
[44]
Yamanashi, Y.; Takada, T.; Kurauchi, R.; Tanaka, Y.; Komine, T.; Suzuki, H. Transporters for the intestinal absorption of cholesterol, vitamin E, and vitamin K. J. Atheroscler. Thromb., 2017, 24(4), 347-359.
[http://dx.doi.org/10.5551/jat.RV16007] [PMID: 28100881]
[45]
Nguyen, D.V.; Drover, V.A.; Knopfel, M.; Dhanasekaran, P.; Hauser, H.; Phillips, M.C. Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption. J. Lipid Res., 2009, 50(11), 2235-2244.
[http://dx.doi.org/10.1194/jlr.M900036-JLR200] [PMID: 19454765]
[46]
Goncalves, A.; Gontero, B.; Nowicki, M.; Margier, M.; Masset, G.; Amiot, M.J.; Reboul, E. Micellar lipid composition affects micelle interaction with class B scavenger receptor extracellular loops. J. Lipid Res., 2015, 56(6), 1123-1133.
[http://dx.doi.org/10.1194/jlr.M057612] [PMID: 25833688]
[47]
Béaslas, O.; Cueille, C.; Delers, F.; Chateau, D.; Chambaz, J.; Rousset, M.; Carrière, V. Sensing of dietary lipids by enterocytes: a new role for SR-BI/CLA-1. PLoS One, 2009, 4(1)e4278
[http://dx.doi.org/10.1371/journal.pone.0004278] [PMID: 19169357]
[48]
Jia, L.; Betters, J.L.; Yu, L. Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu. Rev. Physiol., 2011, 73, 239-259.
[http://dx.doi.org/10.1146/annurev-physiol-012110-142233] [PMID: 20809793]
[49]
Zhang, J.H.; Ge, L.; Qi, W.; Zhang, L.; Miao, H.H.; Li, B.L.; Yang, M.; Song, B.L. The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake. J. Biol. Chem., 2011, 286(28), 25088-25097.
[http://dx.doi.org/10.1074/jbc.M111.244475] [PMID: 21602275]
[50]
Kamishikiryo, J.; Haraguchi, M.; Nakashima, S.; Tasaka, Y.; Narahara, H.; Sugihara, N.; Nakamura, T.; Morita, T. N-terminal domain of the cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) is essential for α-tocopherol transport. Biochem. Biophys. Res. Commun., 2017, 486(2), 476-480.
[http://dx.doi.org/10.1016/j.bbrc.2017.03.065] [PMID: 28315682]
[51]
Temel, R.E.; Gebre, A.K.; Parks, J.S.; Rudel, L.L. Compared with Acyl-CoA:cholesterol O-acyltransferase (ACAT) 1 and lecithin:cholesterol acyltransferase, ACAT2 displays the greatest capacity to differentiate cholesterol from sitosterol. J. Biol. Chem., 2003, 278(48), 47594-47601.
[http://dx.doi.org/10.1074/jbc.M308235200] [PMID: 12975367]
[52]
Field, F.J.; Mathur, S.N. beta-sitosterol: esterification by intestinal acylcoenzyme A: cholesterol acyltransferase (ACAT) and its effect on cholesterol esterification. J. Lipid Res., 1983, 24(4), 409-417.
[PMID: 6854150]
[53]
Lo Sasso, G.; Murzilli, S.; Salvatore, L.; D’Errico, I.; Petruzzelli, M.; Conca, P.; Jiang, Z.Y.; Calabresi, L.; Parini, P.; Moschetta, A. Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis. Cell Metab., 2010, 12(2), 187-193.
[http://dx.doi.org/10.1016/j.cmet.2010.07.002] [PMID: 20674863]
[54]
Hu, X.; Steffensen, K.R.; Jiang, Z.Y.; Parini, P.; Gustafsson, J.A.; Gåfvels, M.; Eggertsen, G. LXRβ activation increases intestinal cholesterol absorption, leading to an atherogenic lipoprotein profile. J. Intern. Med., 2012, 272(5), 452-464.
[http://dx.doi.org/10.1111/j.1365-2796.2012.02529.x] [PMID: 22329358]
[55]
Yu, L.; Gupta, S.; Xu, F.; Liverman, A.D.; Moschetta, A.; Mangelsdorf, D.J.; Repa, J.J.; Hobbs, H.H.; Cohen, J.C. Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. J. Biol. Chem., 2005, 280(10), 8742-8747.
[http://dx.doi.org/10.1074/jbc.M411080200] [PMID: 15611112]
[56]
Wang, J.; Mitsche, M.A.; Lütjohann, D.; Cohen, J.C.; Xie, X.S.; Hobbs, H.H. Relative roles of ABCG5/ABCG8 in liver and intestine. J. Lipid Res., 2015, 56(2), 319-330.
[http://dx.doi.org/10.1194/jlr.M054544] [PMID: 25378657]
[57]
Drobnik, W.; Lindenthal, B.; Lieser, B.; Ritter, M.; Christiansen Weber, T.; Liebisch, G.; Giesa, U.; Igel, M.; Borsukova, H.; Büchler, C.; Fung-Leung, W.P.; Von Bergmann, K.; Schmitz, G. ATP-binding cassette transporter A1 (ABCA1) affects total body sterol metabolism. Gastroenterology, 2001, 120(5), 1203-1211.
[http://dx.doi.org/10.1053/gast.2001.23250] [PMID: 11266384]
[58]
McNeish, J.; Aiello, R.J.; Guyot, D.; Turi, T.; Gabel, C.; Aldinger, C.; Hoppe, K.L.; Roach, M.L.; Royer, L.J.; de Wet, J.; Broccardo, C.; Chimini, G.; Francone, O.L. High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1. Proc. Natl. Acad. Sci. USA, 2000, 97(8), 4245-4250.
[http://dx.doi.org/10.1073/pnas.97.8.4245] [PMID: 10760292]
[59]
Temel, R.E.; Lee, R.G.; Kelley, K.L.; Davis, M.A.; Shah, R.; Sawyer, J.K.; Wilson, M.D.; Rudel, L.L. Intestinal cholesterol absorption is substantially reduced in mice deficient in both ABCA1 and ACAT2. J. Lipid Res., 2005, 46(11), 2423-2431.
[http://dx.doi.org/10.1194/jlr.M500232-JLR200] [PMID: 16150828]
[60]
Iqbal, J.; Parks, J.S.; Hussain, M.M. Lipid absorption defects in intestine-specific microsomal triglyceride transfer protein and ATP-binding cassette transporter A1-deficient mice. J. Biol. Chem., 2013, 288(42), 30432-30444.
[http://dx.doi.org/10.1074/jbc.M113.501247] [PMID: 24019513]
[61]
Cohen, J.C.; Pertsemlidis, A.; Fahmi, S.; Esmail, S.; Vega, G.L.; Grundy, S.M.; Hobbs, H.H. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc. Natl. Acad. Sci. USA, 2006, 103(6), 1810-1815.
[http://dx.doi.org/10.1073/pnas.0508483103] [PMID: 16449388]
[62]
Wang, L.J.; Wang, J.; Li, N.; Ge, L.; Li, B.L.; Song, B.L. Molecular characterization of the NPC1L1 variants identified from cholesterol low absorbers. J. Biol. Chem., 2011, 286(9), 7397-7408.
[http://dx.doi.org/10.1074/jbc.M110.178368] [PMID: 21189420]
[63]
Alrefai, W.A.; Annaba, F.; Sarwar, Z.; Dwivedi, A.; Saksena, S.; Singla, A.; Dudeja, P.K.; Gill, R.K. Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Am. J. Physiol. Gastrointest. Liver Physiol., 2007, 292(1), G369-G376.
[http://dx.doi.org/10.1152/ajpgi.00306.2006] [PMID: 17008555]
[64]
Pramfalk, C.; Jiang, Z.Y.; Cai, Q.; Hu, H.; Zhang, S.D.; Han, T.Q.; Eriksson, M.; Parini, P. HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver. J. Lipid Res., 2010, 51(6), 1354-1362.
[http://dx.doi.org/10.1194/jlr.M900274-JLR200] [PMID: 20460578]
[65]
Iwayanagi, Y.; Takada, T.; Suzuki, H. HNF4alpha is a crucial modulator of the cholesterol-dependent regulation of NPC1L1. Pharm. Res., 2008, 25(5), 1134-1141.
[http://dx.doi.org/10.1007/s11095-007-9496-9] [PMID: 18080173]
[66]
Lee, E.S.; Seo, H.J.; Back, S.S.; Han, S.H.; Jeong, Y.J.; Lee, J.W.; Choi, S.Y.; Han, K. Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1. BMB Rep., 2015, 48(9), 513-518.
[http://dx.doi.org/10.5483/BMBRep.2015.48.9.253] [PMID: 25739390]
[67]
Lin, J.; Shao, W.Q.; Chen, Q.Z.; Zhu, W.W.; Lu, L.; Jia, H.L.; Chen, J.H. Osteopontin deficiency protects mice from cholesterol gallstone formation by reducing expression of intestinal NPC1L1. Mol. Med. Rep., 2017, 16(2), 1785-1792.
[http://dx.doi.org/10.3892/mmr.2017.6774] [PMID: 28627641]
[68]
Armstrong, M.J.; Carey, M.C. Thermodynamic and molecular determinants of sterol solubilities in bile salt micelles. J. Lipid Res., 1987, 28(10), 1144-1155.
[PMID: 3681139]
[69]
Ikeda, I.; Tanaka, K.; Sugano, M.; Vahouny, G.V.; Gallo, L.L. Inhibition of cholesterol absorption in rats by plant sterols. J. Lipid Res., 1988, 29(12), 1573-1582.
[PMID: 2468730]
[70]
Mel’nikov, S.M.; Seijen ten Hoorn, J.W.; Eijkelenboom, A.P. Effect of phytosterols and phytostanols on the solubilization of cholesterol by dietary mixed micelles: an in vitro study. Chem. Phys. Lipids, 2004, 127(2), 121-141.
[http://dx.doi.org/10.1016/j.chemphyslip.2003.09.015] [PMID: 14725996]
[71]
Nissinen, M.; Gylling, H.; Vuoristo, M.; Miettinen, T.A. Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am. J. Physiol. Gastrointest. Liver Physiol., 2002, 282(6), G1009-G1015.
[http://dx.doi.org/10.1152/ajpgi.00446.2001] [PMID: 12016126]
[72]
Mel’nikov, S.M.; Seijen ten Hoorn, J.W.; Bertrand, B. Can cholesterol absorption be reduced by phytosterols and phytostanols via a cocrystallization mechanism? Chem. Phys. Lipids, 2004, 127(1), 15-33.
[http://dx.doi.org/10.1016/j.chemphyslip.2003.08.007] [PMID: 14706738]
[73]
Hui, D.Y.; Howles, P.N. Carboxyl ester lipase: structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis. J. Lipid Res., 2002, 43(12), 2017-2030.
[http://dx.doi.org/10.1194/jlr.R200013-JLR200] [PMID: 12454261]
[74]
Howles, P.N.; Carter, C.P.; Hui, D.Y. Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice. J. Biol. Chem., 1996, 271(12), 7196-7202.
[http://dx.doi.org/10.1074/jbc.271.12.7196] [PMID: 8636157]
[75]
Weng, W.; Li, L.; van Bennekum, A.M.; Potter, S.H.; Harrison, E.H.; Blaner, W.S.; Breslow, J.L.; Fisher, E.A. Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase knockout mice. Biochemistry, 1999, 38(13), 4143-4149.
[http://dx.doi.org/10.1021/bi981679a] [PMID: 10194330]
[76]
Ikeda, I.; Sugano, M. Some aspects of mechanism of inhibition of cholesterol absorption by beta-sitosterol. Biochim. Biophys. Acta, 1983, 732(3), 651-658.
[http://dx.doi.org/10.1016/0005-2736(83)90243-2] [PMID: 6615593]
[77]
Konlande, J.E.; Fisher, H. Evidence for a nonabsorptive antihypercholesterolemic action of phytosterols in the chicken. J. Nutr., 1969, 98(4), 435-442.
[http://dx.doi.org/10.1093/jn/98.4.435] [PMID: 5816510]
[78]
Vanstone, C.A.; Raeini-Sarjaz, M.; Jones, P.J. Injected phytosterols/stanols suppress plasma cholesterol levels in hamsters. J. Nutr. Biochem., 2001, 12(10), 565-574.
[http://dx.doi.org/10.1016/S0955-2863(01)00175-9] [PMID: 12031262]
[79]
Plat, J.; van Onselen, E.N.; van Heugten, M.M.; Mensink, R.P. Effects on serum lipids, lipoproteins and fat soluble antioxidant concentrations of consumption frequency of margarines and shortenings enriched with plant stanol esters. Eur. J. Clin. Nutr., 2000, 54(9), 671-677.
[http://dx.doi.org/10.1038/sj.ejcn.1601071] [PMID: 11002377]
[80]
Matvienko, O.A.; Lewis, D.S.; Swanson, M.; Arndt, B.; Rainwater, D.L.; Stewart, J.; Alekel, D.L. A single daily dose of soybean phytosterols in ground beef decreases serum total cholesterol and LDL cholesterol in young, mildly hypercholesterolemic men. Am. J. Clin. Nutr., 2002, 76(1), 57-64.
[http://dx.doi.org/10.1093/ajcn/76.1.57] [PMID: 12081816]
[81]
Rudkowska, I.; AbuMweis, S.S.; Nicolle, C.; Jones, P.J. Cholesterol-lowering efficacy of plant sterols in low-fat yogurt consumed as a snack or with a meal. J. Am. Coll. Nutr., 2008, 27(5), 588-595.
[http://dx.doi.org/10.1080/07315724.2008.10719742] [PMID: 18845709]
[82]
Calpe-Berdiel, L.; Escolà-Gil, J.C.; Julve, J.; Zapico-Muñiz, E.; Canals, F.; Blanco-Vaca, F. Differential intestinal mucosal protein expression in hypercholesterolemic mice fed a phytosterol-enriched diet. Proteomics, 2007, 7(15), 2659-2666.
[http://dx.doi.org/10.1002/pmic.200600792] [PMID: 17610203]
[83]
Smart, E.J.; De Rose, R.A.; Farber, S.A. Annexin 2-caveolin 1 complex is a target of ezetimibe and regulates intestinal cholesterol transport. Proc. Natl. Acad. Sci. USA, 2004, 101(10), 3450-3455.
[http://dx.doi.org/10.1073/pnas.0400441101] [PMID: 14985510]
[84]
Valasek, M.A.; Weng, J.; Shaul, P.W.; Anderson, R.G.; Repa, J.J. Caveolin-1 is not required for murine intestinal cholesterol transport. J. Biol. Chem., 2005, 280(30), 28103-28109.
[http://dx.doi.org/10.1074/jbc.M504609200] [PMID: 15919660]
[85]
Jesch, E.D.; Seo, J.M.; Carr, T.P.; Lee, J.Y. Sitosterol reduces messenger RNA and protein expression levels of Niemann-Pick C1-like 1 in FHs 74 Int cells. Nutr. Res., 2009, 29(12), 859-866.
[http://dx.doi.org/10.1016/j.nutres.2009.10.016] [PMID: 19963159]
[86]
Jakulj, L.; Trip, M.D.; Sudhop, T.; von Bergmann, K.; Kastelein, J.J.; Vissers, M.N. Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels. J. Lipid Res., 2005, 46(12), 2692-2698.
[http://dx.doi.org/10.1194/jlr.M500260-JLR200] [PMID: 16162943]
[87]
Gomes, G.B.; Zazula, A.D.; Shigueoka, L.S.; Fedato, R.A.; da Costa, A.B.; Guarita-Souza, L.C.; Baena, C.P.; Olandoski, M.; Faria-Neto, J.R. A randomized open-label trial to assess the effect of plant sterols associated with ezetimibe in low-density lipoprotein levels in patients with coronary artery disease on statin therapy. J. Med. Food, 2017, 20(1), 30-36.
[http://dx.doi.org/10.1089/jmf.2016.0042] [PMID: 28098515]
[88]
Lin, X.; Racette, S.B.; Lefevre, M.; Ma, L.; Spearie, C.A.; Steger-May, K.; Ostlund, R.E. Jr. Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans. Circulation, 2011, 124(5), 596-601.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.006692] [PMID: 21768544]
[89]
Calpe-Berdiel, L.; Escolà-Gil, J.C.; Ribas, V.; Navarro-Sastre, A.; Garcés-Garcés, J.; Blanco-Vaca, F. Changes in intestinal and liver global gene expression in response to a phytosterol-enriched diet. Atherosclerosis, 2005, 181(1), 75-85.
[http://dx.doi.org/10.1016/j.atherosclerosis.2004.11.025] [PMID: 15939057]
[90]
Plösch, T.; Kruit, J.K.; Bloks, V.W.; Huijkman, N.C.; Havinga, R.; Duchateau, G.S.; Lin, Y.; Kuipers, F. Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter. J. Nutr., 2006, 136(8), 2135-2140.
[http://dx.doi.org/10.1093/jn/136.8.2135] [PMID: 16857831]
[91]
Field, F.J.; Born, E.; Mathur, S.N. Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick C1-like 1 protein gene expression. J. Lipid Res., 2004, 45(12), 2252-2259.
[http://dx.doi.org/10.1194/jlr.M400208-JLR200] [PMID: 15342687]
[92]
Jain, D.; Ebine, N.; Jia, X.; Kassis, A.; Marinangeli, C.; Fortin, M.; Beech, R.; Hicks, K.B.; Moreau, R.A.; Kubow, S.; Jones, P.J. Corn fiber oil and sitostanol decrease cholesterol absorption independently of intestinal sterol transporters in hamsters. J. Nutr. Biochem., 2008, 19(4), 229-236.
[http://dx.doi.org/10.1016/j.jnutbio.2007.02.012] [PMID: 17601722]
[93]
Méndez-González, J.; Süren-Castillo, S.; Calpe-Berdiel, L.; Rotllan, N.; Vázquez-Carrera, M.; Escolà-Gil, J.C.; Blanco-Vaca, F. Disodium ascorbyl phytostanol phosphate (FM-VP4), a modified phytostanol, is a highly active hypocholesterolaemic agent that affects the enterohepatic circulation of both cholesterol and bile acids in mice. Br. J. Nutr., 2010, 103(2), 153-160.
[http://dx.doi.org/10.1017/S0007114509991656] [PMID: 19822032]
[94]
Field, F.J.; Born, E.; Mathur, S.N. Effect of micellar beta-sitosterol on cholesterol metabolism in CaCo-2 cells. J. Lipid Res., 1997, 38(2), 348-360.
[PMID: 9162754]
[95]
Chang, C.C.; Chen, J.; Thomas, M.A.; Cheng, D.; Del Priore, V.A.; Newton, R.S.; Pape, M.E.; Chang, T.Y. Regulation and immunolocalization of acyl-coenzyme A: cholesterol acyltransferase in mammalian cells as studied with specific antibodies. J. Biol. Chem., 1995, 270(49), 29532-29540.
[http://dx.doi.org/10.1074/jbc.270.49.29532] [PMID: 7493995]
[96]
Ho, S.S.; Pal, S. Margarine phytosterols decrease the secretion of atherogenic lipoproteins from HepG2 liver and Caco2 intestinal cells. Atherosclerosis, 2005, 182(1), 29-36.
[http://dx.doi.org/10.1016/j.atherosclerosis.2005.01.031] [PMID: 16115472]
[97]
Schonewille, M.; Brufau, G.; Shiri-Sverdlov, R.; Groen, A.K.; Plat, J. Serum TG-lowering properties of plant sterols and stanols are associated with decreased hepatic VLDL secretion. J. Lipid Res., 2014, 55(12), 2554-2561.
[http://dx.doi.org/10.1194/jlr.M052407] [PMID: 25348863]
[98]
Honda, A.; Salen, G.; Honda, M.; Batta, A.K.; Tint, G.S.; Xu, G.; Chen, T.S.; Tanaka, N.; Shefer, S. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity is inhibited by cholesterol and up-regulated by sitosterol in sitosterolemic fibroblasts. J. Lab. Clin. Med., 2000, 135(2), 174-179.
[http://dx.doi.org/10.1067/mlc.2000.104459] [PMID: 10695663]
[99]
Fernández, C.; Suárez, Y.; Ferruelo, A.J.; Gómez-Coronado, D.; Lasunción, M.A. Inhibition of cholesterol biosynthesis by Delta22-unsaturated phytosterols via competitive inhibition of sterol Delta24-reductase in mammalian cells. Biochem. J., 2002, 366(Pt 1), 109-119.
[http://dx.doi.org/10.1042/bj20011777] [PMID: 12162789]
[100]
Nguyen, L.B.; Salen, G.; Shefer, S.; Bullock, J.; Chen, T.; Tint, G.S.; Chowdhary, I.R.; Lerner, S. Deficient ileal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in sitosterolemia: sitosterol is not a feedback inhibitor of intestinal cholesterol biosynthesis. Metabolism, 1994, 43(7), 855-859.
[http://dx.doi.org/10.1016/0026-0495(94)90266-6] [PMID: 8028508]
[101]
Salen, G.; Shore, V.; Tint, G.S.; Forte, T.; Shefer, S.; Horak, I.; Horak, E.; Dayal, B.; Nguyen, L.; Batta, A.K. Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. J. Lipid Res., 1989, 30(9), 1319-1330.
[PMID: 2600539]
[102]
Plat, J.; Nichols, J.A.; Mensink, R.P. Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation. J. Lipid Res., 2005, 46(11), 2468-2476.
[http://dx.doi.org/10.1194/jlr.M500272-JLR200] [PMID: 16150823]
[103]
Yang, C.; Yu, L.; Li, W.; Xu, F.; Cohen, J.C.; Hobbs, H.H. Disruption of cholesterol homeostasis by plant sterols. J. Clin. Invest., 2004, 114(6), 813-822.
[http://dx.doi.org/10.1172/JCI22186] [PMID: 15372105]
[104]
Kaneko, E.; Matsuda, M.; Yamada, Y.; Tachibana, Y.; Shimomura, I.; Makishima, M. Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist. J. Biol. Chem., 2003, 278(38), 36091-36098.
[http://dx.doi.org/10.1074/jbc.M304153200] [PMID: 12847102]
[105]
Brauner, R.; Johannes, C.; Ploessl, F.; Bracher, F.; Lorenz, R.L. Phytosterols reduce cholesterol absorption by inhibition of 27-hydroxycholesterol generation, liver X receptor α activation, and expression of the basolateral sterol exporter ATP-binding cassette A1 in Caco-2 enterocytes. J. Nutr., 2012, 142(6), 981-989.
[http://dx.doi.org/10.3945/jn.111.157198] [PMID: 22535758]
[106]
Calpe-Berdiel, L.; Escolà-Gil, J.C.; Blanco-Vaca, F. Phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of ATP-binding cassette transporter A1. Br. J. Nutr., 2006, 95(3), 618-622.
[http://dx.doi.org/10.1079/BJN20051659] [PMID: 16512948]
[107]
Calpe-Berdiel, L.; Escolà-Gil, J.C.; Blanco-Vaca, F. Are LXR-regulated genes a major molecular target of plant sterols/stanols? Atherosclerosis, 2007, 195(1), 210-211.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.11.042] [PMID: 17222851]
[108]
Cedó, L.; Santos, D.; Ludwig, I.A.; Silvennoinen, R.; García-León, A.; Kaipiainen, L.; Carbó, J.M.; Valledor, A.F.; Gylling, H.; Motilva, M.J.; Kovanen, P.T.; Lee-Rueckert, M.; Blanco-Vaca, F.; Escolà-Gil, J.C. Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor. Mol. Nutr. Food Res., 2017, 61(9)
[http://dx.doi.org/10.1002/mnfr.201700055] [PMID: 28296229]
[109]
van der Velde, A.E.; Brufau, G.; Groen, A.K. Transintestinal cholesterol efflux. Curr. Opin. Lipidol., 2010, 21(3), 167-171.
[http://dx.doi.org/10.1097/MOL.0b013e3283395e45] [PMID: 20410820]
[110]
Temel, R.E.; Brown, J.M. A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion. Trends Pharmacol. Sci., 2015, 36(7), 440-451.
[http://dx.doi.org/10.1016/j.tips.2015.04.002] [PMID: 25930707]
[111]
de Boer, J.F.; Schonewille, M.; Dikkers, A.; Koehorst, M.; Havinga, R.; Kuipers, F.; Tietge, U.J.; Groen, A.K. Transintestinal and biliary cholesterol secretion both contribute to macrophage reverse cholesterol transport in rats-brief report. Arterioscler. Thromb. Vasc. Biol., 2017, 37(4), 643-646.
[http://dx.doi.org/10.1161/ATVBAHA.116.308558] [PMID: 28232326]
[112]
Paalvast, Y.; de Boer, J.F.; Groen, A.K. Developments in intestinal cholesterol transport and triglyceride absorption. Curr. Opin. Lipidol., 2017, 28(3), 248-254.
[http://dx.doi.org/10.1097/MOL.0000000000000415] [PMID: 28338522]
[113]
Aye, I.L.; Singh, A.T.; Keelan, J.A. Transport of lipids by ABC proteins: interactions and implications for cellular toxicity, viability and function. Chem. Biol. Interact., 2009, 180(3), 327-339.
[http://dx.doi.org/10.1016/j.cbi.2009.04.012] [PMID: 19426719]
[114]
Le May, C.; Berger, J.M.; Lespine, A.; Pillot, B.; Prieur, X.; Letessier, E.; Hussain, M.M.; Collet, X.; Cariou, B.; Costet, P. Transintestinal cholesterol excretion is an active metabolic process modulated by PCSK9 and statin involving ABCB1. Arterioscler. Thromb. Vasc. Biol., 2013, 33(7), 1484-1493.
[http://dx.doi.org/10.1161/ATVBAHA.112.300263] [PMID: 23559630]
[115]
Vrins, C.L.; Ottenhoff, R.; van den Oever, K.; de Waart, D.R.; Kruyt, J.K.; Zhao, Y.; van Berkel, T.J.; Havekes, L.M.; Aerts, J.M.; van Eck, M.; Rensen, P.C.; Groen, A.K. Trans-intestinal cholesterol efflux is not mediated through high density lipoprotein. J. Lipid Res., 2012, 53(10), 2017-2023.
[http://dx.doi.org/10.1194/jlr.M022194] [PMID: 22802462]
[116]
van der Veen, J.N.; van Dijk, T.H.; Vrins, C.L.; van Meer, H.; Havinga, R.; Bijsterveld, K.; Tietge, U.J.; Groen, A.K.; Kuipers, F. Activation of the liver X receptor stimulates trans-intestinal excretion of plasma cholesterol. J. Biol. Chem., 2009, 284(29), 19211-19219.
[http://dx.doi.org/10.1074/jbc.M109.014860] [PMID: 19416968]
[117]
Jakulj, L.; van Dijk, T.H.; de Boer, J.F.; Kootte, R.S.; Schonewille, M.; Paalvast, Y.; Boer, T.; Bloks, V.W.; Boverhof, R.; Nieuwdorp, M.; Beuers, U.H.; Stroes, E.S.; Groen, A.K. Transintestinal cholesterol transport is active in mice and humans and controls ezetimibe-induced fecal neutral sterol excretion. Cell Metab., 2016, 24(6), 783-794.
[http://dx.doi.org/10.1016/j.cmet.2016.10.001] [PMID: 27818259]
[118]
Vrins, C.L.; van der Velde, A.E.; van den Oever, K.; Levels, J.H.; Huet, S.; Oude Elferink, R.P.; Kuipers, F.; Groen, A.K. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux. J. Lipid Res., 2009, 50(10), 2046-2054.
[http://dx.doi.org/10.1194/jlr.M800579-JLR200] [PMID: 19439761]
[119]
Warrier, M.; Shih, D.M.; Burrows, A.C.; Ferguson, D.; Gromovsky, A.D.; Brown, A.L.; Marshall, S.; McDaniel, A.; Schugar, R.C.; Wang, Z.; Sacks, J.; Rong, X.; Vallim, T.A.; Chou, J.; Ivanova, P.T.; Myers, D.S.; Brown, H.A.; Lee, R.G.; Crooke, R.M.; Graham, M.J.; Liu, X.; Parini, P.; Tontonoz, P.; Lusis, A.J.; Hazen, S.L.; Temel, R.E.; Brown, J.M. The TMAO-generating enzyme flavin monooxygenase 3 is a central regulator of cholesterol balance. Cell Rep., 2015, 10(3), 326-338.
[http://dx.doi.org/10.1016/j.celrep.2014.12.036] [PMID: 25600868]
[120]
de Boer, J.F.; Schonewille, M.; Boesjes, M.; Wolters, H.; Bloks, V.W.; Bos, T.; van Dijk, T.H.; Jurdzinski, A.; Boverhof, R.; Wolters, J.C.; Kuivenhoven, J.A.; van Deursen, J.M.; Oude Elferink, R.P.; Moschetta, A.; Kremoser, C.; Verkade, H.J.; Kuipers, F.; Groen, A.K. Intestinal farnesoid X receptor controls transintestinal cholesterol excretion in mice. Gastroenterology, 2017, 152(5), 1126-1138.e6.
[http://dx.doi.org/10.1053/j.gastro.2016.12.037] [PMID: 28065787]
[121]
van der Velde, A.E.; Vrins, C.L.; van den Oever, K.; Seemann, I.; Oude Elferink, R.P.; van Eck, M.; Kuipers, F.; Groen, A.K. Regulation of direct transintestinal cholesterol excretion in mice. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 295(1), G203-G208.
[http://dx.doi.org/10.1152/ajpgi.90231.2008] [PMID: 18511744]
[122]
Brufau, G.; Kuipers, F.; Lin, Y.; Trautwein, E.A.; Groen, A.K. A reappraisal of the mechanism by which plant sterols promote neutral sterol loss in mice. PLoS One, 2011, 6(6)e21576
[http://dx.doi.org/10.1371/journal.pone.0021576] [PMID: 21738715]
[123]
Jakulj, L.; Besseling, J.; Stroes, E.S.; Groen, A.K. Intestinal cholesterol secretion: future clinical implications. Neth. J. Med., 2013, 71(9), 459-465.
[PMID: 24218419]
[124]
Nguyen, L.B.; Shefer, S.; Salen, G.; Ness, G.C.; Tint, G.S.; Zaki, F.G.; Rani, I. A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. J. Clin. Invest., 1990, 86(3), 923-931.
[http://dx.doi.org/10.1172/JCI114794] [PMID: 2394840]
[125]
Yu, L.; von Bergmann, K.; Lutjohann, D.; Hobbs, H.H.; Cohen, J.C. Selective sterol accumulation in ABCG5/ABCG8-deficient mice. J. Lipid Res., 2004, 45(2), 301-307.
[http://dx.doi.org/10.1194/jlr.M300377-JLR200] [PMID: 14657202]
[126]
Calpe-Berdiel, L.; Escolà-Gil, J.C.; Blanco-Vaca, F. New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. Atherosclerosis, 2009, 203(1), 18-31.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.06.026] [PMID: 18692849]
[127]
Plat, J.; Mensink, R.P. Effects of plant stanol esters on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase mRNA expression in mononuclear blood cells of healthy men and women. FASEB J., 2002, 16(2), 258-260.
[http://dx.doi.org/10.1096/fj.01-0653fje] [PMID: 11772951]
[128]
Volger, O.L.; van der Boom, H.; de Wit, E.C.; van Duyvenvoorde, W.; Hornstra, G.; Plat, J.; Havekes, L.M.; Mensink, R.P.; Princen, H.M. Dietary plant stanol esters reduce VLDL cholesterol secretion and bile saturation in apolipoprotein E*3-Leiden transgenic mice. Arterioscler. Thromb. Vasc. Biol., 2001, 21(6), 1046-1052.
[http://dx.doi.org/10.1161/01.ATV.21.6.1046] [PMID: 11397718]
[129]
Gylling, H.; Miettinen, T.A. Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment. Diabetologia, 1994, 37(8), 773-780.
[http://dx.doi.org/10.1007/BF00404334] [PMID: 7988779]
[130]
Gylling, H.; Miettinen, T.A. Effects of inhibiting choles-terol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. J. Lipid Res., 1996, 37(8), 1776-1785.
[PMID: 8864962]
[131]
Ooi, E.M.; Watts, G.F.; Barrett, P.H.; Chan, D.C.; Clifton, P.M.; Ji, J.; Nestel, P.J. Dietary plant sterols supplementation does not alter lipoprotein kinetics in men with the metabolic syndrome. Asia Pac. J. Clin. Nutr., 2007, 16(4), 624-631.
[PMID: 18042521]
[132]
Thompson, G.R.; Naoumova, R.P.; Watts, G.F. Role of cholesterol in regulating apolipoprotein B secretion by the liver. J. Lipid Res., 1996, 37(3), 439-447.
[PMID: 8728309]
[133]
Ruiu, G.; Pinach, S.; Veglia, F.; Gambino, R.; Marena, S.; Uberti, B.; Alemanno, N.; Burt, D.; Pagano, G.; Cassader, M. Phytosterol-enriched yogurt increases LDL affinity and reduces CD36 expression in polygenic hypercholesterolemia. Lipids, 2009, 44(2), 153-160.
[http://dx.doi.org/10.1007/s11745-008-3259-1] [PMID: 18998188]
[134]
Chiang, J.Y. Bile acids: regulation of synthesis. J. Lipid Res., 2009, 50(10), 1955-1966.
[http://dx.doi.org/10.1194/jlr.R900010-JLR200] [PMID: 19346330]
[135]
Keely, S.J.; Walters, J.R. The Farnesoid X Receptor: Good for BAD. Cell. Mol. Gastroenterol. Hepatol., 2016, 2(6), 725-732.
[http://dx.doi.org/10.1016/j.jcmgh.2016.08.004] [PMID: 28174746]
[136]
Wang, Y.D.; Chen, W.D.; Moore, D.D.; Huang, W. FXR: a metabolic regulator and cell protector. Cell Res., 2008, 18(11), 1087-1095.
[http://dx.doi.org/10.1038/cr.2008.289] [PMID: 18825165]
[137]
Uchida, K.; Takase, H.; Nomura, Y.; Takeda, K.; Takeuchi, N.; Ishikawa, Y. Changes in biliary and fecal bile acids in mice after treatments with diosgenin and beta-sitosterol. J. Lipid Res., 1984, 25(3), 236-245.
[PMID: 6726078]
[138]
Carr, T.P.; Cornelison, R.M.; Illston, B.J.L. S.-P. C.; Gallaherb, D. D. Plant sterols alter bile acid metabolism and reduce cholesterol absorption in hamsters fed a beef-based diet. Nutr. Res., 2002, 22(6), 745-754.
[http://dx.doi.org/10.1016/S0271-5317(02)00389-5]
[139]
Normén, L.; Dutta, P.; Lia, A.; Andersson, H. Soy sterol esters and beta-sitostanol ester as inhibitors of cholesterol absorption in human small bowel. Am. J. Clin. Nutr., 2000, 71(4), 908-913.
[http://dx.doi.org/10.1093/ajcn/71.4.908] [PMID: 10731496]
[140]
Miettinen, T.A.; Vuoristo, M.; Nissinen, M.; Järvinen, H.J.; Gylling, H. Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine. Am. J. Clin. Nutr., 2000, 71(5), 1095-1102.
[http://dx.doi.org/10.1093/ajcn/71.5.1095] [PMID: 10799370]
[141]
Weststrate, J.A.; Ayesh, R.; Bauer-Plank, C.; Drewitt, P.N. Safety evaluation of phytosterol esters. Part 4. Faecal concentrations of bile acids and neutral sterols in healthy normolipidaemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine. Food Chem. Toxicol., 1999, 37(11), 1063-1071.
[http://dx.doi.org/10.1016/S0278-6915(99)00102-7] [PMID: 10566877]
[142]
Baumgartner, S.; Mensink, R.P.; Smet, E.; Konings, M.; Fuentes, S.; de Vos, W.M.; Plat, J. Effects of plant stanol ester consumption on fasting plasma oxy(phyto)sterol concentrations as related to fecal microbiota characteristics. J. Steroid Biochem. Mol. Biol., 2017, 169, 46-53.
[http://dx.doi.org/10.1016/j.jsbmb.2016.02.029] [PMID: 26940357]
[143]
Shefer, S.; Salen, G.; Nguyen, L.; Batta, A.K.; Packin, V.; Tint, G.S.; Hauser, S. Competitive inhibition of bile acid synthesis by endogenous cholestanol and sitosterol in sitosterolemia with xanthomatosis. Effect on cholesterol 7 alpha-hydroxylase. J. Clin. Invest., 1988, 82(6), 1833-1839.
[http://dx.doi.org/10.1172/JCI113799] [PMID: 3143743]
[144]
El Kasmi, K.C.; Anderson, A.L.; Devereaux, M.W.; Vue, P.M.; Zhang, W.; Setchell, K.D.; Karpen, S.J.; Sokol, R.J. Phytosterols promote liver injury and Kupffer cell activation in parenteral nutrition-associated liver disease. Sci. Transl. Med., 2013, 5(206)206ra137
[http://dx.doi.org/10.1126/scitranslmed.3006898] [PMID: 24107776]
[145]
Hu, J.; Zhang, Z.; Shen, W.J.; Azhar, S. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones. Nutr. Metab. (Lond.), 2010, 7, 47.
[http://dx.doi.org/10.1186/1743-7075-7-47] [PMID: 20515451]
[146]
Kovanen, P.T.; Goldstein, J.L.; Chappell, D.A.; Brown, M.S. Regulation of low density lipoprotein receptors by adrenocorticotropin in the adrenal gland of mice and rats in vivo. J. Biol. Chem., 1980, 255(12), 5591-5598.
[PMID: 6247339]
[147]
Rigotti, A.; Edelman, E.R.; Seifert, P.; Iqbal, S.N.; DeMattos, R.B.; Temel, R.E.; Krieger, M.; Williams, D.L. Regulation by adrenocorticotropic hormone of the in vivo expression of scavenger receptor class B type I (SR-BI), a high density lipoprotein receptor, in steroidogenic cells of the murine adrenal gland. J. Biol. Chem., 1996, 271(52), 33545-33549.
[http://dx.doi.org/10.1074/jbc.271.52.33545] [PMID: 8969220]
[148]
Sanders, D.J.; Minter, H.J.; Howes, D.; Hepburn, P.A. The safety evaluation of phytosterol esters. Part 6. The comparative absorption and tissue distribution of phytosterols in the rat. Food Chem. Toxicol., 2000, 38(6), 485-491.
[http://dx.doi.org/10.1016/S0278-6915(00)00021-1] [PMID: 10828500]
[149]
Yu, L.; Hammer, R.E.; Li-Hawkins, J.; Von Bergmann, K.; Lutjohann, D.; Cohen, J.C.; Hobbs, H.H. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc. Natl. Acad. Sci. USA, 2002, 99(25), 16237-16242.
[http://dx.doi.org/10.1073/pnas.252582399] [PMID: 12444248]
[150]
Mushtaq, T.; Wales, J.K.; Wright, N.P. Adrenal insufficiency in phytosterolaemia. Eur. J. Endocrinol., 2007, 157(Suppl. 1), S61-S65.
[http://dx.doi.org/10.1530/EJE-07-0222] [PMID: 17785700]
[151]
Aringer, L.; Eneroth, P.; Nordström, L. Side-chain cleavage of 4-cholesten-3-one, 5-cholesten-3 alpha-ol, beta-sitosterol, and related steroids in endocrine tissues from rat and man. J. Steroid Biochem., 1979, 11(3), 1271-1285.
[http://dx.doi.org/10.1016/0022-4731(79)90196-1] [PMID: 513749]
[152]
Arthur, J.R.; Blair, H.A.; Boyd, G.S.; Mason, J.I.; Suckling, K.E. Oxidation of cholesterol and cholesterol analogues by mitochondrial preparations of steroid-hormone-producing tissue. Biochem. J., 1976, 158(1), 47-51.
[http://dx.doi.org/10.1042/bj1580047] [PMID: 986816]
[153]
Morisaki, M.; Duque, C.; Ikekawa, N.; Shikita, M. Substrate specificity of adrenocortical cytochrome P-450scc--I. Effect of structural modification of cholesterol side-chain on pregnenolone production. J. Steroid Biochem., 1980, 13(5), 545-550.
[http://dx.doi.org/10.1016/0022-4731(80)90211-3] [PMID: 7392631]
[154]
Liu, F.; Chen, J.; Shi, F.; Wang, T.; Watanabe, G.; Taya, K. Phytosterol additive boosts adrenal response to ACTH in male Japanese quail (Coturnix coturnix japonica). Endocrine, 2012, 41(2), 338-341.
[http://dx.doi.org/10.1007/s12020-011-9590-y] [PMID: 22212440]

Rights & Permissions Print Cite
Article Metrics
104
14
1
2
World Chagas Disease
© 2024 Bentham Science Publishers | Privacy Policy