Abstract 16934: UC1002, a Carboxyl Ester Lipase Inhibitor, Raises HDL in CETP Transgenic Mice and Increases Reverse Cholesterol Transport, and Also Lowers LDL and VLDL in Mice Fed Western Diet

Background: Raising HDL and increasing reverse cholesterol transport (RCT) are believed to lower cardiovascular risk independently of decreasing LDL. We recently documented increased RCT in carboxyl ester lipase (CEL) knockout mice by a mechanism that involves both increased biliary transport of HDL cholesteryl ester and lack of cholesteryl ester hydrolysis in intestine. We have also shown that lack of CEL in mice expressing CETP raises serum HDL due to increased hepatic production. Objective: To test the efficacy of CEL inhibitor, UC1002, with respect to increasing RCT and raising HDL in CETP transgenic mice; to test the efficacy of UC1002 in reversing hyperlipidemia in Western diet-fed CETP transgenic mice. Methods: Wild type C57BL/6 mice or C57BL/6 mice with a CETP transgene were given UC1002 daily for 2 weeks in chow at doses of 50-150 mg/kg b.w. (n = 6-12). Sterol excretion was measured before and after treatment or was measured in control groups fed normal chow. HDL was measured by heparin/Mn precip...