HDL biology
CETP raises HDL triglyceride but leaves triglyceride production and clearance unchanged in APOE*3-Leiden mice (J Lipid Res 2010)
Original title: CETP does not affect triglyceride production or clearance in APOE*3-Leiden mice
Comparing APOE*3-Leiden (E3L) mice with and without expression of the human CETP gene, plasma lipid levels on chow were comparable between male and female E3L and E3L.CETP mice, though CETP expression increased triglyceride levels within the HDL fraction. CETP did not affect the postprandial plasma triglyceride response, hepatic VLDL-triglyceride or VLDL-apoB production rate, plasma triglyceride clearance rate, or organ-specific triglyceride uptake after infusion of VLDL-like emulsion particles, and did not affect weight gain on a high-fat diet. The CETP-induced rise in HDL triglyceride is therefore not explained by changes in triglyceride production or tissue-specific clearance, despite CETP's known role in worsening atherosclerosis in this hyperlipidemic model.
Original abstract
The cholesteryl ester transfer protein (CETP) facilitates the bidirectional transfer of cholesteryl esters and triglycerides (TG) between HDL and (V)LDL. By shifting cholesterol in plasma from HDL to (V)LDL in exchange for VLDL-TG, CETP aggravates atherosclerosis in hyperlipidemic APOE*3-Leiden (E3L) mice. The aim of this study was to investigate the role of CETP in TG metabolism and high-fat diet-induced obesity by using E3L mice with and without the expression of the human CETP gene. On chow, plasma lipid levels were comparable between both male and female E3L and E3L.CETP mice. Further mechanistic studies were performed using male mice. CETP expression increased the level of TG in HDL. CETP did not affect the postprandial plasma TG response or the hepatic VLDL-TG and VLDL-apolipoprotein B production rate. Moreover, CETP did not affect the plasma TG clearance rate or organ-specific TG uptake after infusion of VLDL-like emulsion particles. In line with the absence of an effect of CETP on tissue-specific TG uptake, CETP also did not affect weight gain in response to a high-fat diet. In conclusion, the CETP-induced increase of TG in the HDL fraction of E3L mice is not associated with changes in the production of TG or with tissue-specific clearance of TG from the plasma.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.