HDL biology
Combining apoA-II and CETP transgenes triggers massive VLDL overproduction in mice (J Lipid Res 2001)
Original title: ApoA-II expression in CETP transgenic mice increases VLDL production and impairs VLDL clearance
To study how apoA-II, a major HDL protein of largely unknown metabolic role, interacts with CETP, researchers crossbred human apoA-II transgenic mice with CETP transgenic mice. On an atherogenic diet, CETP x apoA-II double-transgenic mice had 2-fold lower HDL-cholesterol and a proportionally similar rise in total plasma cholesterol, free cholesterol, non-HDL cholesterol, and free fatty acids compared with CETP-transgenic mice alone, along with a striking 112-fold increase in plasma triglycerides, mainly carried in protein-enriched VLDL. This triglyceride rise reflected both higher VLDL production than either single-transgenic strain or non-transgenic controls, and reduced VLDL catabolism specifically compared with CETP-transgenic mice, establishing CETP x apoA-II-transgenic mice as a model for studying VLDL overproduction and implicating both proteins in VLDL metabolism regulation.
Original abstract
Apolipoprotein (apo)A-II is a major high density lipoprotein (HDL) protein; however, its role in lipoprotein metabolism is largely unknown. Transgenic (Tg) mice that overexpress human apoA-II present functional lecithin: cholesterol acyltransferase deficiency, HDL deficiency, hypertriglyceridemia and, when fed an atherogenic diet, increased non-HDL cholesterol and increased susceptibility to atherosclerosis. In contrast to humans, mice do not present cholesteryl ester transfer protein (CETP) activity in plasma. To study the in vivo interaction of these two proteins, we crossbred human apoA-II and CETP-Tg mice. CETP x apoA-II-Tg mice fed an atherogenic diet, compared with CETP-Tg mice presented a 2-fold decrease in HDL cholesterol and a quantitatively similar increase in total plasma cholesterol and percentage of free cholesterol, non-HDL cholesterol, and free fatty acids, together with a remarkable 112-fold increase in plasma triglycerides. Plasma triglycerides in CETP x apoA-II-Tg mice were mainly associated with very low density lipoproteins (VLDL), which were also enriched in protein content, and resulted from a combination of higher production rate compared with both of their progenitors and non-Tg control mice, and decreased catabolism compared only with CETP-Tg mice. These results show CETP x apoA-II-Tg mice to be a good model with which to study mechanisms leading to VLDL overproduction and suggest that CETP and, in particular apoA-II, may play a role in the regulation of VLDL metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.