Differential effects of gemfibrozil and fenofibrate on reverse cholesterol transport from macrophages to feces in vivo

Noemí Rotllan, Gemma Llaverías, Josep Julve, Matti Jauhiainen, Laura Calpe-Berdiel, Cristina Hernández, Rafael Simó, Francisco Blanco-Vaca, Joan Carles Escolà-Gil

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26 Citations (Scopus)

Abstract

Gemfibrozil and fenofibrate, two of the fibrates most used in clinical practice, raise HDL cholesterol (HDLc) and are thought to reduce the risk of atherosclerotic cardiovascular disease. These drugs act as PPARα agonists and upregulate the expression of genes crucial in reverse cholesterol transport (RCT). In the present study, we determined the effects of these two fibrates on RCT from macrophages to feces in vivo in human apoA-I transgenic (hApoA-ITg) mice. [3H]cholesterol-labeled mouse macrophages were injected intraperitoneally into hApoA-ITg mice treated with intragastric doses of fenofibrate, gemfibrozil or a vehicle solution for 17 days, and radioactivity was determined in plasma, liver and feces. Fenofibrate, but not gemfibrozil, enhanced [3H]cholesterol flux to plasma and feces of female hApoA-ITg mice. Fenofibrate significantly increased plasma HDLc, HDL phospholipids, hApoA-I levels and phospholipid transfer protein activity, whereas these parameters were not altered by gemfibrozil treatment. Unlike gemfibrozil, fenofibrate also induced the generation of larger HDL particles, which were more enriched in cholesteryl esters, together with higher potential to generate preβ-HDL formation and caused a significant increase in [ 3H]cholesterol efflux to plasma. Our findings demonstrate that fenofibrate promotes RCT from macrophages to feces in vivo and, thus, highlight a differential action of this fibrate on HDL. © 2010 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)104-110
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1811
Issue number2
DOIs
Publication statusPublished - 1 Feb 2011

Keywords

  • apoA-I
  • Atherosclerosis
  • Cardiovascular disease
  • Fibrate
  • HDL
  • PPAR-alpha

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