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


RESULTS
We 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.


CONCLUSIONS
Our 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.
Bencharif
Karima
K
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.
Hoareau
Laurence
L
Murumalla
Ravi K
RK
Tarnus
Evelyne
E
Tallet
Frank
F
Clerc
Roger G
RG
Gardes
Christophe
C
Cesari
Maya
M
Roche
Régis
R
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D016632:Apolipoprotein A-I / Q000502:physiology*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008875:Middle Aged; D015290:Second Messenger Systems / Q000187:drug effects; D055571:Secretory Pathway / Q000187:drug effects; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D002784:Cholesterol; D000242:Cyclic AMP; D006903:Hydroxymethylglutaryl CoA Reductases