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

Abstract

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. Conclusion. 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. © 2010 Bencharif et al.