Effect of apoA-I on cholesterol release and apoE secretion in human mature adipocytes

Lipids in Health and Disease

Research

Evelyne Tarnus¹  Ravi K Murumalla¹  Maya Cesari¹  Régis Roche¹  Karima Bencharif¹  Laurence Hoareau¹  Roger G Clerc²  Christophe Gardes²  Frank Tallet³ 

[1] LBGM-GEICO, Laboratoire de Biochimie et de Génétique Moléculaire - Groupe d'Etude sur l'Inflammation Chronique et l'Obésité, Plateforme CYROI, Université de La Réunion 15 avenue René Cassin 97715 Saint Denis Messag Cedex 9, France;Metabolic Disease Therapeutic Area, F. Hoffmann-La Roche Ltd., 124 Grenzacherstrasse, 4070 Basel, Switzerland;Service de biochimie, Centre Hospitalier Félix Guyon, 97400, Saint Denis, Ile de La Réunion, France;

关键词: Cholesterol;    Simvastatin;    Forskolin;    Cholesterol Efflux;    Intracellular cAMP;   

DOI  :  10.1186/1476-511X-9-75

 received in 2010-06-10, accepted in 2010-07-20,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe risk of cardiovascular disease is inversely correlated to level of plasma HDL-c. Moreover, reverse cholesterol transport (RCT) from peripheral tissues to the liver is the most widely accepted mechanism linked to the anti-atherosclerotic activity of HDL. The apolipoprotein A-I (apoA-I) and the ABC transporters play a key role in this process.Adipose tissue constitutes the body's largest pool of free cholesterol. The adipose cell could therefore be regarded as a key factor in cholesterol homeostasis. The present study investigates the capacity of primary cultures of mature human adipocytes to release cholesterol and explores the relationships between apoA-I, ABCA1, and apoE as well as the signaling pathways that could be potentially involved.ResultsWe demonstrate that apoA-I induces a strong increase in cholesterol release and apoE secretion from adipocytes, whereas it has no transcriptional effect on ABCA1 or apoE genes. Furthermore, brefeldin A (BFA), an intracellular trafficking inhibitor, reduces basal cholesterol and apoE secretion, but does not modify induction by apoA-I. The use of statins also demonstrates that apoA-I stimulated cholesterol release is independent of HMG-CoA reductase activation.ConclusionOur work highlights the fact that adipose tissue, and particularly adipocytes, may largely contribute to RCT via a mechanism specifically regulated within these cells. This further supports the argument that adipose tissue must be regarded as a major factor in the development of cardiovascular diseases, in particular atherosclerosis.

【 授权许可】

Unknown   
© Bencharif et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.