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

Journal of Nutrition

Volumn 142, Issue 6, 2012, Pages 981-989

  Brauner, Reinhard ^a   Johannes, Christian ^a   Ploessl, Florian ^b   Bracher, Franz ^b   Lorenz, Reinhard L ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

26 HYDROXYCHOLESTEROL; ABC TRANSPORTER A1; CAMPESTEROL; CHOLESTEROL; LIVER X RECEPTOR ALPHA; OXYSTEROL; PHYTOSTEROL; SITOSTEROL;

ARTICLE; CHOLESTEROL METABOLISM; CONTROLLED STUDY; DRUG EFFECT; HUMAN; HUMAN CELL; INTESTINE CELL; LIVER CELL; MACROPHAGE; PROTEIN EXPRESSION;

ABSORPTION; ATP-BINDING CASSETTE TRANSPORTERS; CACO-2 CELLS; CHOLESTEROL; ENTEROCYTES; GENE EXPRESSION REGULATION; HEP G2 CELLS; HEPATOCYTES; HUMANS; HYDROXYCHOLESTEROLS; MACROPHAGES; ORPHAN NUCLEAR RECEPTORS; PHYTOSTEROLS;

EID: 84863557427     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.111.157198     Document Type: Article

References (54)

1. Ostlund RE Jr. Phytosterols in human nutrition. Annu Rev Nutr. 2002;22:533-49.
2. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000;290:1771-5.
3. Graf GA, Yu L, Li WP, Gerard R, Tuma PL, Cohen JC, Hobbs HH. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem. 2003;278:48275-82.
4. Igel M, Giesa U, Lutjohann D, von Bergmann K. Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice. J Lipid Res. 2003;44:533-8.
5. Yu L, von Bergmann K, Lutjohann D, Hobbs HH, Cohen JC. Selective sterol accumulation in ABCG5/ABCG8-deficient mice. J Lipid Res. 2004;45:301-7.
6. Yu L, Hammer RE, Li-Hawkins J, von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci USA. 2002;99:16237-42.
7. Wang J, Zhang DW, Lei Y, Xu F, Cohen JC, Hobbs HH, Xie XS. Purification and reconstitution of sterol transfer by native mouse ABCG5 and ABCG8. Biochemistry. 2008;47:5194-204.
8. Wang J, Sun F, Zhang DW, Ma Y, Xu F, Belani JD, Cohen JC, Hobbs HH, Xie XS. Sterol transfer by ABCG5 and ABCG8: in vitro assay and reconstitution. J Biol Chem. 2006;281:27894-904.
9. Kielar D, Dietmaier W, Langmann T, Aslanidis C, Probst M, Naruszewicz M, Schmitz G. Rapid quantification of human ABCA1 mRNA in various cell types and tissues by real-time reverse transcription-PCR. Clin Chem. 2001;47:2089-97.
10. Bodzioch M, Orso E, Klucken J, Langmann T, Bottcher A, Diederich W, Drobnik W, Barlage S, Buchler C, Porsch-Ozcurumez M, et al. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat Genet. 1999;22:347-51.
11. McNeish J, Aiello RJ, Guyot D, Turi T, Gabel C, Aldinger C, Hoppe KL, Roach ML, Royer LJ, de Wet J, et al. 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; 97:4245-50.
12. Lütjohann D, von Bergmann K. Phytosterolaemia: diagnosis, characterization and therapeutical approaches. Ann Med. 1997;29:181-4.
13. Schwartz K, Lawn RM, Wade DP. ABC1 gene expression and ApoA-Imediated cholesterol efflux are regulated by LXR. Biochem Biophys Res Commun. 2000;274:794-802.
14. Zhang Y, Mangelsdorf DJ. LuXuRies of lipid homeostasis: the unity of nuclear hormone receptors, transcription regulation, and cholesterol sensing. Mol Interv. 2002;2:78-87.
15. Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, Shan B, Heyman RA, Dietschy JM, Mangelsdorf DJ. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science. 2000;289:1524-9.
16. Schmitz G, Langmann T. Structure, function and regulation of the ABC1 gene product. Curr Opin Lipidol. 2001;12:129-40.
17. Ohama T, Hirano K, Zhang Z, Aoki R, Tsujii Ki, Nakagawa-Toyama Y, Tsukamoto K, Ikegami C, Matsuyama A, Ishigami M, et al. Dominant expression of ATP-binding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands. Biochem Biophys Res Commun. 2002;296:625-30.
18. Murthy S, Born E, Mathur SN, Field FJ. LXR/RXR activation enhances basolateral efflux of cholesterol in CaCo-2 cells. J Lipid Res. 2002; 43:1054-64.
19. Folch J, Lees M, Stanley GHS. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226:497-509.
20. Björkhem I, Andersson O, Diczfalusy U, Sevastik B, Xiu R, Duan C, Lund E. Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages. Proc Natl Acad Sci USA. 1994;91:8592-6.
21. Aringer L, Eneroth P, Nordstrom L. Side chain hydroxylation of cholesterol, campesterol and beta- sitosterol in rat liver mitochondria. J Lipid Res. 1976;17:263-72.
22. Johannes C, Lorenz RL. Preparation and mass spectrometry of 14 pure and 18O(2)-labeled oxidation products from the phytosterols betasitosterol and stigmasterol. Anal Biochem. 2004;325:107-16.
23. Fu X, Menke JG, Chen Y, Zhou G, MacNaul KL, Wright SD, Sparrow CP, Lund EG. 27-Hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem. 2001;276:38378-87.
24. Hanes CS. Studies on plant amylases: the effect of starch concentration upon the velocity of hydrolysis by the amylase of germinated barley. Biochem J. 1932;26:1406-21.
25. Plat J, Mensink RP. Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FASEB J. 2002;16:1248-53.
26. Quinn CM, Jessup W, Wong J, Kritharides L, Brown AJ. Expression and regulation of sterol 27-hydroxylase (CYP27A1) in human macrophages: a role for RXR and PPARgamma ligands. Biochem J. 2005;385:823-30.
27. Szakács G, Annereau JP, Lababidi S, Shankavaram U, Arciello A, Bussey KJ, Reinhold W, Guo Y, Kruh GD, Reimers M, et al. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell. 2004;6:129-37.
28. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402-8.
29. Yamanashi Y, Takada T, Suzuki H. Niemann-Pick C1-Like 1 overexpression facilitates ezetimibe-sensitive cholesterol and beta-sitosterol uptake in CaCo-2 cells. J Pharmacol Exp Ther. 2007;320:559-64.
30. Davis HR Jr, Zhu LJ, Hoos LM, Tetzloff G, Maguire M, Liu J, Yao X, Iyer SP, Lam MH, Lund EG, et al. 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; 279:33586-92.
31. Salen G, von Bergmann K, Lutjohann D, Kwiterovich P, Kane J, Patel SB, Musliner T, Stein P, Musser B. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation. 2004;109:966-71.
32. Lütjohann D, Bjorkhem I, Beil UF, von Bergmann K. Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment. J Lipid Res. 1995;36:1763-73.
33. Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, Hobbs HH. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest. 2002;110:671-80.
34. Temel RE, Gebre AK, Parks JS, Rudel LL. 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;278:47594-601.
35. Iqbal J, Anwar K, Hussain MM. Multiple, independently regulated pathways of cholesterol transport across the intestinal epithelial cells. J Biol Chem. 2003;278:31610-20.
36. Brunham LR, Kruit JK, Iqbal J, Fievet C, Timmins JM, Pape TD, Coburn BA, Bissada N, Staels B, Groen AK, et al. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest. 2006; 116:1052-62.
37. Field FJ, Born E, Mathur SN. LXR/RXR ligand activation enhances basolateral efflux of beta-sitosterol in CaCo-2 cells. J Lipid Res. 2004; 45:905-13.
38. Tachibana S, Hirano M, Hirata T, Matsuo M, Ikeda I, Ueda K, Sato R. Cholesterol and plant sterol efflux from cultured intestinal epithelial cells is mediated by ATP-binding cassette transporters. Biosci Biotechnol Biochem. 2007;71:1886-95.
39. Takahashi K, Kimura Y, Kioka N, Matsuo M, Ueda K. Purification and ATPase activity of human ABCA1. J Biol Chem. 2006;281:10760-8.
40. Song C, Liao S. Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha. Endocrinology. 2000;141:4180-4.
41. Nguyen LB, Shefer S, Salen G, Tint SG, Batta AK. Competitive inhibition of hepatic sterol 27-hydroxylase by sitosterol: decreased activity in sitosterolemia. Proc Assoc Am Physicians. 1998;110:32-9.
42. Janowski BA, Willy PJ, Devi TR, Falck JR,Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 1996;383:728-31.
43. Chen W, Chen G, Head DL, Mangelsdorf DJ, Russell DW. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab. 2007;5:73-9.
44. 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;278:36091-8.
45. Plat J, Nichols JA, Mensink RP. Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation. J Lipid Res. 2005;46:2468-76.
46. Brown JM, Yu L. Opposing gatekeepers of apical sterol transport: Niemann-Pick C1-Like 1 (NPC1L1) and ATP-binding cassette transporters G5 and G8 (ABCG5/ABCG8). Immunol Endocr Metab Agents Med Chem. 2009;9:18-29.
47. Plösch T, Bloks VW, Terasawa Y, Berdy S, Siegler K, Van Der SF, Kema IP, Groen AK, Shan B, Kuipers F, et al. Sitosterolemia in ABCtransporter G5-deficient mice is aggravated on activation of the liver-X receptor. Gastroenterology. 2004;126:290-300.
48. Yu L, York J, von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J Biol Chem. 2003;278:15565-70.
49. Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem. 2002;277:18793-800.
50. Jia X, Ebine N, Demonty I, Wang Y, Beech R, Muise V, Fortin MG, Jones PJ. Hypocholesterolaemic effects of plant sterol analogues are independent of ABCG5 and ABCG8 transporter expressions in hamsters. Br J Nutr. 2007;98:550-5.
51. Repa JJ, Lund EG, Horton JD, Leitersdorf E, Russell DW, Dietschy JM, Turley SD. Disruption of the sterol 27-hydroxylase gene in mice results in hepatomegaly and hypertriglyceridemia. J Biol Chem. 2000;275: 39685-92.
52. Demonty I, Ras RT, van der Knaap HC, Duchateau GS, Meijer L, Zock PL, Geleijnse JM, Trautwein EA. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr. 2009;139:271-84.
53. Marangoni F, Poli A. Phytosterols and cardiovascular health. Pharmacol Res. 2010;61:193-9.
54. Weingärtner O, Lütjohann D, Ji S, Weisshoff N, List F, Sudhop T, von Bergmann K, Gertz K, König J, Schäfers HJ, et al. Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol. 2008;51: 1553-61.