HDL biology
Adding CETP shifts lipoproteins toward VLDL and IDL/LDL, and appears to blunt diabetes-driven hyperlipidemia in LPL-deficient mice (J Lipid Res 2002)
Original title: Lipoprotein lipase deficiency and CETP in streptozotocin-treated apoB-expressing mice
Crossing mice expressing human apoB (HuB) with LPL-heterozygous-deficient (LPL1) mice and human CETP transgenic mice on a Western diet, HuB/LPL1 mice had increased VLDL triglyceride, while HuB/LPL1/CETP mice instead had decreased HDL and increased VLDL and IDL/LDL. After streptozotocin-induced diabetes, HuB and HuB/LPL1/CETP mice showed no change in lipid profiles or atherosclerosis, whereas STZ-treated HuB/LPL1 mice became more severely diabetic, developed marked hyperlipidemia from increased VLDL and IDL/LDL cholesterol and triglyceride, and showed more atherosclerosis. Adding the CETP transgene to the LPL-deficient background thus reshapes baseline lipoproteins and appears to prevent the diabetes-induced hyperlipidemia and atherosclerosis seen in LPL-deficient mice alone.
Original abstract
Both hyperglycemia and hyperlipidemia have been postulated to increase atherosclerosis in patients with diabetes mellitus. To study the effects of diabetes on lipoprotein profiles and atherosclerosis in a rodent model, we crossed mice that express human apolipoprotein B (HuB), mice that have a heterozygous deletion of lipoprotein lipase (LPL1), and transgenic mice expressing human cholesteryl ester transfer protein (CETP). Lipoprotein profiles due to each genetic modification were assessed while mice were consuming a Western type diet. Fast-protein liquid chromatography analysis of plasma samples showed that HuB/LPL1 mice had increased VLDL triglyceride, and HuB/LPL1/CETP mice had decreased HDL and increased VLDL and IDL/LDL. All strains of mice were made diabetic using streptozotocin (STZ); diabetes did not alter lipid profiles or atherosclerosis in HuB or HuB/LPL1/CETP mice. In contrast, STZ-treated HuB/LPL1 mice were more diabetic, severely hyperlipidemic due to increased cholesterol and triglyceride in VLDL and IDL/LDL, and had more atherosclerosis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.