Display options
Cite
Balendiran GK, Verma M, Perry E. Chemistory of Fibrates. Curr Chem Biol. 2007;1(3):311-316doi: 10.2174/187231307781662198.
Balendiran, G. K., Verma, M., & Perry, E. (2007). Chemistory of Fibrates. Current chemical biology, 1(3), 311-316. https://doi.org/10.2174/187231307781662198
Balendiran, Ganesaratnam K, et al. "Chemistory of Fibrates." Current chemical biology vol. 1,3 (2007): 311-316. doi: https://doi.org/10.2174/187231307781662198
Balendiran GK, Verma M, Perry E. Chemistory of Fibrates. Curr Chem Biol. 2007 Sep;1(3):311-316. doi: 10.2174/187231307781662198. PMID: 34485047; PMCID: PMC8412053.
Copy Download .nbib Format: NLM
Share it on

Curr Chem Biol. 2007 Sep;1(3):311-316. doi: 10.2174/187231307781662198.

Chemistory of Fibrates.

Current chemical biology

Ganesaratnam K Balendiran, Malkhey Verma, Elise Perry

Affiliations

  1. Beckman Research Institute and City of Hope National Medical Center, 1450 E. Duarte Road, Duarte, CA 91010, USA.

PMID: 34485047 PMCID: PMC8412053 DOI: 10.2174/187231307781662198

Abstract

Since the description of the synthetic chemical clofibrate in 1962, various derivatives of fibrates with a diversity of chemical structures have been developed. Several of these are used clinically to treat dyslipidemia because they are generally effective in lowering elevated plasma triglycerides and cholesterol. Studies suggest that several biochemical mechanisms underlie fibrate-mediated modulation of lipoprotein and related metabolites. These mechanisms are: 1) induced lipoprotein lipolysis; 2) induced hepatic fatty acid uptake and reduced hepatic triglyceride formation; 3) amplified removal of low density lipoprotein (LDL) particles; 4) reduced neutral lipid (cholesteryl ester and triglyceride) exchange between very low density lipoprotein (VLDL) and high density lipoprotein (HDL) resulting from decreased plasma levels of triglyceride-rich lipoprotein (TRL); and 5) increased HDL production and stimulation of reverse cholesterol transport. Recent studies of structure-based inhibitor design strategy revealed that an independent enzyme, aldose reductase (AR), is a target of fibrate activity, an additional biochemical mechanism. AR has been implicated as a major player in the development of diabetes and diabetic complications because of its ability to catalyze the conversion of glucose to sorbitol. This article discusses various targets of fibrate action, biochemical pathways and commonalities in potential molecular interactions.

Keywords: Aldose reductase; fibrates; glucose; mechanism; peroxisome proliferation; polyol pathway; sorbitol

References

  1. Biochem Pharmacol. 2005 Nov 25;70(11):1653-63 - PubMed
  2. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6803-8 - PubMed
  3. Nature. 1998 Sep 10;395(6698):137-43 - PubMed
  4. Arch Pathol. 1975 Apr;99(4):181-4 - PubMed
  5. J Biol Chem. 1997 Nov 7;272(45):28210-7 - PubMed
  6. Structure. 1997 May 15;5(5):601-12 - PubMed
  7. Diabetes. 1998 Apr;47(4):507-14 - PubMed
  8. Am J Kidney Dis. 2001 Dec;38(6):1398-407 - PubMed
  9. Lancet. 1962 Jun 23;1(7243):1323-6 - PubMed
  10. Nephrol Dial Transplant. 2000 Sep;15(9):1446-9 - PubMed
  11. Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003 - PubMed
  12. Metabolism. 2005 Dec;54(12):1620-5 - PubMed
  13. Proteins. 2004 Jun 1;55(4):792-804 - PubMed
  14. Curr Opin Lipidol. 2002 Feb;13(1):33-40 - PubMed
  15. Diabetes. 2002 Dec;51(12):3486-91 - PubMed
  16. Arterioscler Thromb. 1993 May;13(5):702-11 - PubMed
  17. Am J Clin Nutr. 1995 Apr;61(4):787-91 - PubMed
  18. Atherosclerosis. 1976 May-Jun;23(3):563-8 - PubMed
  19. BMJ. 2002 Nov 16;325(7373):1139 - PubMed
  20. J Clin Invest. 1991 Dec;88(6):2059-66 - PubMed
  21. J Biol Chem. 1974 Aug 25;249(16):5153-62 - PubMed
  22. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1747-51 - PubMed
  23. Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):12-9 - PubMed
  24. Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):763-72 - PubMed
  25. Atherosclerosis. 1989 Jun;77(2-3):139-49 - PubMed
  26. Eur Heart J. 1998 Feb;19 Suppl A:A24-30 - PubMed
  27. Curr Opin Cell Biol. 1997 Apr;9(2):222-32 - PubMed
  28. Curr Mol Med. 2001 Dec;1(6):633-53 - PubMed
  29. Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):115-21 - PubMed
  30. Eur J Clin Invest. 1974 Jun;4(3):163-74 - PubMed
  31. Eur J Clin Pharmacol. 1983;25(1):57-63 - PubMed
  32. J Mol Med (Berl). 2005 Oct;83(10):774-85 - PubMed
  33. Am J Cardiol. 2000 Sep 1;86(5):547-9, A9 - PubMed
  34. Atherosclerosis. 1982 Sep;44(3):355-65 - PubMed
  35. Int J Clin Pract. 2003 Apr;57(3):249-51 - PubMed
  36. Arterioscler Thromb. 1994 May;14(5):679-85 - PubMed
  37. Mol Cell Endocrinol. 2002 Jul 31;193(1-2):71-9 - PubMed
  38. J Lipid Res. 1996 May;37(5):907-25 - PubMed
  39. J Biol Chem. 1952 Jan;194(1):435-43 - PubMed
  40. Pharmacol Rev. 1998 Mar;50(1):21-33 - PubMed
  41. J Biol Chem. 1982 Jun 10;257(11):6509-17 - PubMed
  42. FASEB J. 2002 Jan;16(1):123-5 - PubMed
  43. Atherosclerosis. 1978 Jun;30(2):147-52 - PubMed
  44. Atherosclerosis. 1992 Mar;93(1-2):83-94 - PubMed
  45. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13919-24 - PubMed
  46. J Biol Chem. 2003 Oct 17;278(42):40859-66 - PubMed
  47. J Clin Invest. 1995 Feb;95(2):705-12 - PubMed
  48. Am J Clin Nutr. 1993 Nov;58(5 Suppl):754S-765S - PubMed
  49. J Biol Chem. 1995 Aug 18;270(33):19269-76 - PubMed
  50. Am J Med. 1987 Nov 27;83(5B):44-9 - PubMed
  51. Am J Physiol. 1998 Jul;275(1):H75-83 - PubMed
  52. Arterioscler Thromb. 1994 Aug;14(8):1327-36 - PubMed
  53. Science. 1975 Nov 21;190(4216):787-9 - PubMed
  54. J Biol Chem. 1977 May 10;252(9):2998-3002 - PubMed
  55. J Lipid Res. 1984 Dec 15;25(13):1577-85 - PubMed
  56. J Clin Endocrinol Metab. 2003 Aug;88(8):3738-46 - PubMed
  57. Annu Rev Biochem. 1995;64:235-57 - PubMed
  58. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5306-11 - PubMed
  59. J Nutr. 1982 Aug;112(8):1546-54 - PubMed
  60. Circulation. 1998 Nov 10;98(19):2088-93 - PubMed
  61. J Lipid Res. 1998 Jul;39(7):1335-48 - PubMed
  62. Am J Cardiol. 2001 Dec 20;88(12A):14N-18N - PubMed
  63. Circulation. 2000 May 23;101(20):2411-7 - PubMed
  64. Mol Cell. 2001 Jan;7(1):161-71 - PubMed
  65. Endocrinology. 2004 Feb;145(2):548-55 - PubMed

Publication Types

Grant support