Dependent and can either be up or down regulated. For instance ox-LDL-CD36 interaction up regulates a PPARc-dependent CD36 gene expression in monocytes-macrophages whereas interaction with FA down regulates gene expression and protein synthesis in enterocytes, but can up regulate the gene in adipocytes. In addition, CD36 may or may not be associated with companion molecules. The Vitronectin Indiplon receptor VNR, caveolin-1, the Intestinal alkaline phosphatase IAP, the CD9 tetraspanin and the Toll-receptor complex show molecular and functional associations with CD36 at the surface of cells. Therefore, genetic expression and molecular functions of CD36 are complex and controlled by membrane and tissue specific molecular associations and different cellular specific signaling pathways. This pleiotropic effect may reasonably well question the clinical relevance and safety of CD36. While the cellular functions of CD36 are recognized, its importance in the physiopathology is less well understood and often controversial. The role of CD36 in the formation of foam cells and the growth of atherosclerotic plaques is well documented. Yet the role of CD36 as a target to combat 349085-38-7 atherosclerosis was criticized. Similarly, evidences supporting a role of CD36 in intestinal fat absorption are accumulated, but contradictory observations have also been reported concerning its direct implication in intestinal lipid trafficking and the control of postprandial hypertriglyceridemia. For instance, CD36 is expressed all through the intestinal tract and is important for the metabolism and the secretion of chylomicron into the lymph. The molecule is required for efficient intestinal absorption of LCFA and VLCFA. Yet, CD36 deficient mice exhibit a normal level of FA absorption and gene deletion does not affect LCFA uptake and TG re-esterification in mouse jejunum. Therefore the potential of CD36 as a therapeutic target is debated. In the present paper we have identified small chemical molecules which have the capacity to inhibit the FA and ox-LDL receptor function of CD36. These inhibitors were able to rescue well characterized animal models from postprandial hypertriglyceridemia and atherosclerosis with a concomitant improvement of insulin resistance and glucose tolerance. The CD36-inhibitor
