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

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.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.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.Epidemiological studies have repeatedly highlighted a strong inverse correlation between plasma concentrations of high-density lipoprotein cholesterol (HDL-c) and the risk of developing cardiovascular diseases, in particular atherosclerosis, in humans. Thus, low levels of plasma HDL-c increase the cardiovascular risk factor [1]. Reverse cholesterol transport (RCT) from peripheral tissues to the liver is a physiological process that enables the negative regulation of cholesterol deposits via the very low-density and low-density lipoprotein (VLDL and LDL). During reverse transport, high-density lipoproteins (HDL) take up cholesterol from peripheral cells and carry it to the liver. This process constitutes an initial and crucial step in cholesterol homeostasis in mammals, especially sinc