Yukimasa Azuma, Jiro Seto, Katsutoshi Ohno, Hiroshi Mikami, Toshihiro
Yamada, Masahiro Yamasaki, Masaru Chiba and Yoichi Nobuhara
Central Research Institute, Nissin Food Products Co., Ltd., 2247, Noji, Kusatsu, Shiga 525-0055, Japan
Abstract: The effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on cholesterol absorption was investigated. NTE-122 inhibited whole-cell ACAT activity in CaCo-2 cells, a human intestinal cell line, with an IC50 value of 4.7 nM. In CaCo-2 cells cultured on a membrane filter, NTE-122 pronouncedly inhibited the basolateral secretion of newly synthesized cholesteryl esters, and significantly reduced the basolateral secretion of newly synthesized triglycerides without influencing the cellular triglyceride synthesis. Furthermore, NTE-122 (1 mg/kg, p.o.) inhibited [14C]cholesterol absorption in rats. These results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects by reducing the absorption of dietary cholesterol.
Keywords: NTE-122, Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, Cholesterol absorption