Patterns of cholesterol metabolism: Pathophysiological and therapeutic implications for dyslipidemias and the metabolic syndrome

Nutrition, Metabolism and Cardiovascular Diseases

Volumn 21, Issue 9, 2011, Pages 620-627

  Lupattelli, G ^a   De Vuono, S ^a   Mannarino, E ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

Author keywords

Metabolic syndrome; Non cholesterol sterols; Primary dyslipidemias

Indexed keywords

BIOLOGICAL MARKER; CAMPESTEROL; CHOLESTANOL; CHOLESTEROL; DRUG DERIVATIVE; PHYTOSTEROL; SITOSTEROL; SITOSTEROL DERIVATIVE;

BLOOD; DYSLIPIDEMIA; HUMAN; LIPID METABOLISM; METABOLIC SYNDROME X; METABOLISM; PATHOPHYSIOLOGY; REVIEW;

BIOLOGICAL MARKERS; CHOLESTANOL; CHOLESTEROL; DYSLIPIDEMIAS; HUMANS; LIPID METABOLISM; METABOLIC SYNDROME X; PHYTOSTEROLS; SITOSTEROLS;

EID: 80052724732     PISSN: 09394753     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.numecd.2011.04.010     Document Type: Review

References (70)

1. Dietschy J.M., Turley S.D., Spady D.K. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res 1993, 34:1637-1659.
2. Cohen D.E. Balancing cholesterol synthesis and absorption in the gastrointestinal tract. J Clin Lipidol 2008, 2:S1-S3.
3. Bosner M.S., Lange L.G., Stenson W.F., Ostlund R.E. Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry. J Lipid Res 1999, 40:302e8.
4. Altmann S.W. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004, 303:1201-1204.
5. 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.
6. Tardif J.C., Grégoire J., L'Allier P.L., Anderson T.J., Bertrand O., Reeves F., et al. Avasimibe and progression of lesions on ultraSound (A-PLUS) investigators. Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerosis lesions. Circulation 2004, 110:3372-3377.
7. Levy E., Spahis S., Sinnett D., Peretti N., Maupas-Schwalm F., Delvin E., et al. Intestinal cholesterol transport proteins: an update and beyond. Curr Opin Lipidol 2007, 18:310-318.
8. Yu L., Li-Hawkins J., Hammer R.E., et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 2002, 110:671-680.
9. Jakulj L., Vissers M.N., Tanck M.W., Hutten B.A., Stellaard F., Kastelein J.J., et al. ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis. J Lipid Res 2010, 51:3016-3023.
10. Oram J.F., Heinecke J.W. ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol Rev 2005, 85:1343-1372.
11. Miettinen T.A., Tilvis R.S., Kesäniemi Y.A. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 1990, 131:20-31.
12. Gylling H., Miettinen T.A. Inheritance of cholesterol metabolism of probands with high or low cholesterol absorption. J Lipid Res 2002, 43:1472-1476.
13. Davis H.R., Zhu L.J., Hoos L.M., et al. Niemann-Pick C1 Like1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole body cholesterol homeostasis. J Biol Chem 2004, 279:33586-33592.
14. Berge K.E., Tian H., Graf G.A., Yu L., Grishin N.V., Schultz J., et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000, 290:1771-1775.
15. Escurriol V., Cofán M., Serra M., Bulló M., Basora J., Salas-Salvadó J., et al. Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet. Eur J Nutr 2009 Sep, 48(6):373-382. Epub 2009 May 3.
16. Gylling H., Hallikainen M., Nissinen M.J., Simonen P., Miettinen T.A. Very high plant stanol intake and serum plant stanols and non-cholesterol sterols. Eur J Nutr 2010 Mar, 49(2):111-117.
17. Agren J.J., Tvrzicka E., Nenonen M.T., Helve T., Hänninen O. Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis. Br J Nutr 2001 Feb, 85(2):137-139.
18. Hallikainen M., Toppinen L., Mykkänen H., Agren J.J., Laaksonen D.E., Miettinen T.A., et al. Interaction between cholesterol and glucose metabolism during dietary carbohydrate modification in subjects with the metabolic syndrome. Am J Clin Nutr 2006 Dec, 84(6):1385-1392.
19. Cohen J.C., Pertsemlidis A., Fahmi S., Esmail S., Vega G.L., Grundy S.M., et al. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci U S A 2006, 103:1810e5.
20. Berge K.E., von Bergmann K., Lutjohann D., Guerra R., Grundy S.M., Hobbs H.H., et al. Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J Lipid Res 2002, 43:486e94.
21. Kesaniemi Y.A., Ehnholm C., Miettinen T.A. Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. Eur J Clin Invest 1987, 80:578e81.
22. Von Bergmann K., Lütjohann D., Lindenthal B., Steinmetz A. Efficiency of intestinal cholesterol absorption in humans is not related to apo E phenotype. J Lipid Res 2003, 44:193e7.
23. Wolff E., Vergnes M.F., Defoort C., Planells R., Portugal H., Nicolay A., et al. Cholesterol absorption status and fasting plasma cholesterol are modulated by the microsomal triacylglycerol transfer protein -493 G/T polymorphism and the usual diet in women. Genes Nutr 2011 Feb, 6(1):71-79.
24. Veerkamp M.J., de Graaf J., Hendriks J.C., Demacker P.N., Stalenhoef A.F. Nomogram to diagnose familial combined hyperlipidemia on the basis of results of a 5-year follow-up study. Circulation 2004, 109:2980-2985.
25. Durrington P. Dyslipidaemia. Lancet 2003 Aug 30, 362(9385):717-731. Review.
26. van Himbergen T.M., Otokozawa S., Matthan N.R., Schaefer E.J., Buchsbaum A., Ai M., et al. Familial combined hyperlipidemia is associated with alterations in the cholesterol synthesis pathway. Arterioscler Thromb Vasc Biol 2010 Jan, 30(1):113-120.
27. García-Otín A.L., Cofán M., Junyent M., Recalde D., Cenarro A., Pocoví M., et al. Increased intestinal cholesterol absorption in autosomal dominant hypercholesterolemia and no mutations in the low-density lipoprotein receptor or apolipoprotein B genes. J Clin Endocrinol Metab 2007, 92:3667-3673.
28. Lupattelli G., Pirro M., Siepi D., Mannarino M.R., Roscini A.R., Vaudo G., et al. Non-cholesterol sterols in different forms of primary hyperlipemias. Nutr Metab Cardiovasc Dis 2010 Aug 11.
29. Yu L., York J., von Bergmann K., Lutjohann D., Cohen J.C., Hobbs H.H. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J Biol Chem 2003, 278:15565-15570.
30. Raal F.J., Santos R.D., Blom D.J., Marais A.D., Charng M.J., Cromwell W.C., et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 2010, 375:998-1006.
31. Cuchel M., Bloedon L.T., Szapary P.O., Kolansky D.M., Wolfe M.L., Sarkis A., et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007, 356:148-156.
32. Borén J., Ekström U., Agren B., Nilsson-Ehle P., Innerarity T.L. The molecular mechanism for the genetic disorder familial defective apolipoprotein B100. J Biol Chem 2001, 276:9214-9218.
33. Soufi M., Sattler A.M., Maerz W., Starke A., Herzum M., Maisch B., et al. A new but frequent mutation of apoB-100-apoB His3543Tyr. Atherosclerosis 2004, 174:11-16.
34. Abifadel M., Varret M., Rabès J.P., Allard D., Ouguerram K., Devillers M., et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003, 34:154-156.
35. Cunningham D., Danley D.E., Geoghegan K.F., Griffor M.C., Hawkins J.L., Subashi T.A., et al. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol 2007, 14:413-419.
36. Zhao Z., Tuakli-Wosornu Y., Lagace T.A., Kinch L., Grishin N.V., Horton J.D., et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 2006, 79:514-523.
37. Cameron J., Holla O.L., Ranheim T., Kulseth M.A., Berge K.E., Leren T.P. Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet 2006, 15:1551-1558.
38. Careskey H.E., Davis R.A., Alborn W.E., Troutt J.S., Cao G., Konrad R.J. Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res 2008, 49:394-398.
39. Berge K.E., Tian H., Graf G.A., Yu L., Grishin N.V., Schultz J., et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000, 290:1771-1775.
40. Hubacek J.A., Berge K.E., Cohen J.C., Hobbs H.H. Mutations in ATP cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia. Hum Mutat 2001, 18:359-360.
41. Alberti K.G., Eckel R.H., Grundy S.M., Zimmet P.Z., Cleeman J.I., Donato K.A., International Diabetes Federation Task Force on Epidemiology and Prevention, National Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, et al. Harmonizing the metabolic syndrome. Circulation 2009, 120:1640-1645.
42. Gylling H., Miettinen T.A. Cholesterol absorption, synthesis, and LDL metabolism in NIDDM. Diabetes Care 1997, 20:90-95.
43. Simonen P., Gylling H., Howard A.N., Miettinen T.A. Introducing a new component of the metabolic syndrome: low cholesterol absorption. Am J Clin Nutr 2000, 72:82-88.
44. Pihlajamäki J., Gylling H., Miettinen T.A., Laakso M. Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. J Lipid Res 2004, 45:507-512.
45. Miettinen T.A., Gylling H., Subgroup analysis of Scandinavian Simvastatin Survival Study (4S) Blood glucose and the metabolism of cholesterol in coronary patients with and without simvastatin treatment. Clin Chim Acta 2007, 379:53-58.
46. Peltola P., Pihlajamäki J., Koutnikova H., Ruotsalainen E., Salmenniemi U., Vauhkonen I., et al. Visceral obesity is associated with high levels of serum squalene. Obesity (Silver Spring) 2006, 14:1155-1163.
47. Chan D.C., Watts G.F., Barrett P.H., O'Neill F.H., Thompson G.R. Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome. Obes Res 2003, 11:591-596.
48. Cofán M., Escurriol V., García-Otín A.L., Moreno-Iribas C., Larrañaga N., Sánchez M.J., et al. Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study. Nutr Metab Cardiovasc Dis 2010 May 27.
49. Gylling H., Hallikainen M., Pihlajamäki J., Agren J., Laakso M., Rajaratnam R.A., et al. Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity. J Lipid Res 2004, 45:1660-1665.
50. Kotronen A., Westerbacka J., Bergholm R., Pietiläinen K.H., Yki-Järvinen H. Liver fat in the metabolic syndrome. J Clin Endocrinol Metab 2007, 92:3490-3497.
51. Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol 2008, 9:125-138.
52. Simonen P., Kotronen A., Hallikainen M., Sevastianova K., Makkonen J., Hakkarainen A., et al. Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity. J Hepatol 2011, 54:153-159.
53. Caballero F., Fernández A., De Lacy A.M., Fernández-Checa J.C., Caballería J., García-Ruiz C. Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. J Hepatol 2009, 50:789-796.
54. Miettinen T.A., Gylling H., Strandberg T., Sarna S. Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ 1998, 316:1127-1130.
55. Matthan N.R., Pencina M., LaRocque J.M., Jacques P.F., D'Agostino R.B., Schaefer E.J., et al. Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J Lipid Res 2009, 50:1927-1935.
56. Silbernagel G., Fauler G., Renner W., Landl E.M., Hoffmann M.M., Winkelmann B.R., et al. The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J Lipid Res 2009, 50:334-341.
57. Silbernagel G., Fauler G., Hoffmann M.M., Lütjohann D., Winkelmann B.R., Boehm B.O., et al. The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality. J Lipid Res 2010, 5:2384-2393.
58. Miettinen T.A., Gylling H., Hallikainen M., Juonala M., Räsänen L., Viikari J., et al. Relation of non-cholesterol sterols to coronary risk factors and carotid intima-media thickness: the Cardiovascular Risk in Young Finns Study. Atherosclerosis 2010, 209:592-597.
59. Miettinen T.A., Gylling H. Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment. Eur J Clin Invest 2003, 33:976-982.
60. Matthan N.R., Resteghini N., Robertson M., Ford I., Shepherd J., Packard C., PROSPER Group, et al. Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial. J Lipid Res 2010, 51:202-209.
61. van Himbergen T.M., Matthan N.R., Resteghini N.A., Otokozawa S., Ai M., Stein E.A., et al. Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers. J Lipid Res 2009, 50:730-739.
62. Tremblay A.J., Lamarche B., Lemelin V., Hoos L., Benjannet S., Seidah N.G., et al. Atorvastatin increases intestinal expression of NPC1L1 in hyperlipidemic men. J Lipid Res 2010 Dec 1.
63. Nissinen M.J., Miettinen T.E., Gylling H., Miettinen T.A. Applicability of non-cholesterol sterols in predicting response in cholesterol metabolism to simvastatin and fluvastatin treatment among hypercholesterolemic men. Nutr Metab Cardiovasc Dis 2010, 20:308-316.
64. Matthan N.R., Giovanni A., Schaefer E.J., Brown B.G., Lichtenstein A.H. Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL. J Lipid Res 2003, 44:800-806.
65. Bertolotti M., Del Puppo M., Gabbi C., Corna F., Carulli L., Pellegrini E., et al. Correlation between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic patients. Steroids 2008, 73:1197-1202.
66. Assmann G., Kannenberg F., Ramey D.R., Musliner T.A., Gutkin S.W., Veltri E.P. Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia. Curr Med Res Opin 2008, 24:249-259.
67. 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, 46:2692-2698.
68. Jakulj L., Vissers M.N., Groen A.K., Hutten B.A., Lutjohann D., Veltri E.P., et al. Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial. J Lipid Res 2010, 51:755-762.
69. Mannarino E., Pirro M., Cortese C., Lupattelli G., Siepi D., Mezzetti A., et al. Effects of a phytosterol-enriched dairy product on lipids, sterols and 8-isoprostane in hypercholesterolemic patients: a multicenter Italian study. Nutr Metab Cardiovasc Dis 2009, 19:84-90.
70. Gylling H., Miettinen T.A. Baseline intestinal absorption and synthesis of cholesterol regulate its response to hypolipidaemic treatments in coronary patients. Atherosclerosis 2002, 160:477-481.