CETP expression enhances liver HDL-cholesteryl ester uptake but does not alter VLDL and biliary lipid secretion

Abstract

The aim of this work was to study how CETP expression affects whole body cholesterol homeostasis. Thus, tissue uptake and plasma removal rates of labeled HDL-cholesteryl ester (CE), VLDL secretion rates, and biliary lipid secretion and fecal bile acid content were compared between human CETP transgenic (Tg) and non-transgenic (nTg) mice fed with a standard diet. CETP Tg mice exhibited increased HDL-CE plasma fractional catabolic rate and uptake by the liver, adrenals, adipose tissue and spleen. HDL fractions from both CETP Tg and from nTg mice were removed faster from the plasma of CETP expressing than from nTg mice, suggesting a direct role of CETP in accelerating tissue CE uptake. However, neither hepatic output of VLDL cholesterol and triglycerides nor biliary lipid and fecal bile acid excretion were changed in CETP Tg compared to nTg mice. CETP Tg mice also showed enhanced hepatic cholesterol content. Steady state cholesterol homeostasis was probably preserved through the downregulation of hepatic HMG-CoA reductase and LDL receptor expression. In conclusion, although CETP expression facilitates cholesteryl ester tissue uptake, it does not alter biliary lipid and fecal bile acid excretion, the mandatory final step of the reverse cholesterol transport.