Torcetrapib
Torcetrapib boosts reverse cholesterol transport by 118 percent in obese, insulin-resistant transgenic mice (Clin Transl Sci 2011)
Original title: CETP inhibitor torcetrapib promotes reverse cholesterol transport in obese insulin-resistant CETP-ApoB100 transgenic mice
Because insulin resistance and type 2 diabetes are linked to low HDL cholesterol that may impair reverse cholesterol transport (RCT), researchers tested torcetrapib in CETP-apolipoprotein B100 transgenic mice made obese and insulin resistant with a 60% high-fat diet for 3 months. The high-fat diet raised body weight by 30% and the insulin-resistance index by 846%, raised total cholesterol by 46%, and lowered the HDL-cholesterol-to-total-cholesterol ratio by 28% (all p < 0.05 or better). Compared with vehicle, torcetrapib 30 mg per kg per day for 3 weeks raised HDL cholesterol and the HDL-to-total-cholesterol ratio by 41% and 37%, increased macrophage cholesterol efflux by 22%, and increased in vivo RCT by 118% as measured by tritiated bile acid fecal excretion, with total fecal bile acid mass rising 158% (p < 0.01 or better for all), demonstrating that CETP inhibition improves reverse cholesterol transport even under obese, insulin-resistant conditions.
Original abstract
Insulin resistance and type 2 diabetes are associated with low HDL-cholesterol (HDL-c) levels, which would impair reverse cholesterol transport (RCT). A promising therapeutic strategy is to raise HDL with cholesteryl ester transfer protein (CETP) inhibitors, but their effects on RCT remains to be demonstrated in vivo. We therefore evaluated the effects of CETP inhibitor torcetrapib in CETP-apolipoprotein (apo)B100 mice made obese and insulin resistant with a 60% high-fat diet. High-fat diet over 3 months increased body weight and homeostasis model of insulin resistance index by 30% and 846%, respectively (p < 0.01 for both vs. chow-fed mice). Total cholesterol (TC) increased by 46% and HDL-c/TC ratio decreased by 28% (both p < 0.05). Compared to vehicle, high-fat-fed mice treated with torcetrapib (30 mg/kg/day, 3 weeks) showed increased HDL-c levels and HDL-c/TC ratio by 41% and 37% (both p < 0.05). Torcetrapib increased in vitro macrophage cholesterol efflux by 22% and in vivo RCT through a 118% increase in (3) H-bile acids fecal excretion after (3) H-cholesterol labeled macrophage injection (p < 0.01 for both). Fecal total bile acids mass was also increased by 158% (p < 0.001). In conclusion, CETP inhibition by torcetrapib improves RCT in CETP-apoB100 mice. These results emphasize the potential of CETP inhibition to prevent cardiovascular diseases.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.