As previously reported, triacsin C, a selective inhibitor of acyl-CoA synthetase, inhibited the synthesis of cholesteryl ester and triacylglycerol in mouse peritoneal macrophages, leading to a reduction of lipid droplets. Therefore, the in vivo efficacy was studied. Low-density lipoprotein receptor-knockout (LDLR-/-) mice were fed a high cholesterol diet (0.15%) for two months to measure the atherogenic areas of the hearts and aortas. When triacsin C was orally administered (10 mg/kg/day), the atherosclerotic areas were significantly reduced by 86% in aorta and 36% in hearts. The results strongly suggested that triacsin C shows anti-atherogenic activity by inhibiting acyl-CoA synthetase activity.
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