Effects of fibrate drugs on expression of ABCA1 and HDL biogenesis in hepatocytes

J Cardiovasc Pharmacol. 2008 Mar;51(3):258-66. doi: 10.1097/FJC.0b013e3181624b22.


Fibric acid-shaped drugs raise high-density lipoprotein (HDL) cholesterol by upregulating the HDL-related genes through activating peroxisome proliferater activated receptor (PPAR)-alpha. We investigated the effects of fibrates to induce expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and increase HDL biogenesis in hepatocytes. Fenofibrate, bezafibrate, gemfibrozil, and LY518674 were tested for HepG2 cells and primary-cultured mouse hepatocytes. All the compounds examined increased ABCA1 expression and HDL biogenesis dependent on PPARalpha in association with the liver X receptor alpha upregulation. While fenofibrate and LY518674 showed exclusive dependency on PPARalpha for these activities, bezafibrate and gemfibrozil exhibited dependency on PPARbeta/delta and PPARgamma as well. On the other hand, cholesterol-enrichment of HDL may involve PPARgamma for fenofibrate and bezafibrate, and PPARbeta/delta for the fibrates examined except for bezafibrate. We concluded that fibrates enhance expression of ABCA1 in hepatocytes to contribute to increase of the HDL biogenesis in a PPAR-dependent manner, whether exclusively or nonexclusively on PPARalpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / drug effects*
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Bezafibrate / pharmacology
  • Blotting, Western
  • Cells, Cultured
  • Fenofibrate / pharmacology
  • Gemfibrozil / pharmacology
  • Gene Expression Regulation / drug effects
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hypolipidemic Agents / pharmacology*
  • Lipoproteins, HDL / biosynthesis
  • Lipoproteins, HDL / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peroxisome Proliferator-Activated Receptors / drug effects
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Propionates / pharmacology
  • Triazoles / pharmacology


  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Hypolipidemic Agents
  • LY 518674
  • Lipoproteins, HDL
  • Peroxisome Proliferator-Activated Receptors
  • Propionates
  • Triazoles
  • Gemfibrozil
  • Fenofibrate
  • Bezafibrate