To protect against the growth of atherosclerotic Th-1165a plaque at an in vivo concentration compatible with the in vitro activity of this molecule. Reduction of the 517-28-2 cost plasma level of TG was however unexpected because CD36-deficient mice were reported to have increased levels of plasma TG. To verify that this result was not model specific and was not due to the double knock-out of both the LDL-R and leptin genes in the DKO mouse model, the effect of anti-CD36 molecule on plasma TG concentration was examined in an independent diabetic fructose fed rat model. Results that summarize these experiments are illustrated in Figure 5. When administrated at concentration ranging from 0.1 to 10 mg/kg AP5055 was able to produce a similar dose dependent reduction of the plasma TG within weeks of treatment. When using the ZDF rat model, AP5258 produced a significant reduction of the TG plasma concentration. The inactive analog AP5156 had no effect. Therefore, the decrease in plasma TG correlated with the cellular activity of the compounds and was not model or analog dependent. Differences in the potency of these molecules in the different models were however observed. This may be explained by the relative stringency of the different models in terms of metabolic syndrome, the ZDF rat being less sensitive to the treatment than the mouse or the fructose fed rat model. Alternatively, the two compounds may have different metabolism. In the present study, correlation between the anti-CD36 inhibitor activity of small molecular weight chemicals and the known pathophysiological activity of this scavenger receptor were established. Although different mechanisms may be involved in the oral versus IP activity of these inhibitors, both administrations were able to improve the metabolic profile of defined and independent rodent models. A significant reduction of the plasma concentration of triglycerides and a better glucose usage were observed at pharmacological doses with a concomitant reduction of the atherosclerotic and diabetic consequences of these attributes. CD36 is a well characterized FA translocase and an oxidized LDL receptor expressed in many cell types including macrophages, adipocytes, endothelial cells and enterocytes. Expression of this gene is ligand-bind
