HDL biology
CETP expression completely abolishes LXR-agonist-induced HDL enlargement in mice (J Biol Chem 2003)
Original title: Enlargement of high density lipoprotein in mice via liver X receptor activation requires apolipoprotein E and is abolished by cholesteryl ester transfer protein expression
To identify the factors that generate the larger HDL1 and HDLc particles seen after treatment with the synthetic liver X receptor (LXR) agonist T0901317, researchers treated apoE-deficient, CETP-transgenic, and wild-type mice with varying doses of the agonist and monitored HDL by fast protein liquid chromatography, apolipoprotein analysis, electron microscopy, and nondenaturing gel electrophoresis. In apoE knockout mice, the LXR agonist induced neither larger HDL formation nor increased HDL cholesterol, showing apoE is essential for the effect; apoE-deficient mice also showed a significant LXR-agonist-driven increase in VLDL/LDL cholesterol and apoB content. In CETP transgenic mice, CETP expression completely abolished LXR-agonist-mediated HDL enlargement and greatly reduced the HDL cholesterol increase. The authors conclude apoE and CETP are both directly and intimately involved in the formation of enlarged HDL1/HDLc particles in mice.
Original abstract
The factors involved in the generation of larger high density lipoprotein (HDL) particles, HDL1 and HDLc, are still not well understood. Administration of a specific synthetic liver X receptor (LXR) agonist, T0901317, in mice resulted in an increase of not only HDL cholesterol but also HDL particle size (Cao, G., Beyer, T. P., Yang, X. P., Schmidt, R. J., Zhang, Y., Bensch, W. R., Kauffman, R. F., Gao, H., Ryan, T. P., Liang, Y., Eacho, P. I., and Jiang, X. C. (2002) J. Biol. Chem. 277, 39561-39565). We have investigated the roles that apoE and CETP may play in this process. We treated apoE-deficient, cholesterol ester transport protein (CETP) transgenic, and wild type mice with various doses of the LXR agonist and monitored their HDL levels. Fast protein liquid chromatography and apolipoprotein analysis revealed that in apoE knockout mouse plasma, there was neither induction of larger HDL formation nor increase of HDL cholesterol, suggesting that apoE is essential for the LXR agonist effects on HDL metabolism. In CETP transgenic mice, CETP expression completely abolished LXR agonist-mediated HDL enlargement and greatly attenuated HDL cholesterol levels. Analysis of HDL particles by electron microscope and nondenaturing gel electrophoresis revealed similar findings. In apoE-deficient mice, LXR agonist also produced a significant increase in very low density lipoprotein/low density lipoprotein cholesterol and apolipoprotein B content. Our studies provide direct evidence that apoE and CETP are intimately involved in the accumulation of the enlarged HDL (HDL1 or HDLc) particles in mice.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.