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

Abstract:

: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.

journal_name

J Cardiovasc Pharmacol

authors

Hossain MA,Tsujita M,Gonzalez FJ,Yokoyama S

doi

10.1097/FJC.0b013e3181624b22

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

258-66

issue

3

eissn

0160-2446

issn

1533-4023

pii

00005344-200803000-00007

journal_volume

51

pub_type

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