Decreased post-prandial triglyceride response and diminished remnant lipoprotein formation in cholesteryl ester transfer protein (CETP) deficiency

Plasma cholesteryl ester transfer protein (CETP) mediates CE/TG exchange among various lipoproteins. CETP deficiency results in low LDL and high HDL phenotype including apoE-rich large HDL. Large HDL could provide apoE to chylomicron/VLDL during lipolysis in post-prandial state, accelerating remnant lipoprotein uptake in the liver. To determine the effects of low CETP levels on post-prandial lipoprotein metabolism, lipid levels of plasma remnant-like lipoprotein particles (RLP) fraction were determined in one homozygous and three heterozygous CETP deficiency and controls with apoE3/3 phenotype. After oral fat-load, the area under curve (AUC) of TG levels were remarkably decreased in CETP deficiency as compared to controls (423 +/- 187 [S.D.] mg/dl x h in three heterozygous CETP deficiency and 926 +/- 268 [S.D.] in 10 controls, P=0.012). Similarly, the homozygote had a low AUC of TG levels (416 mg/dl x h). Plasma RLP-cholesterol levels were decreased in heterozygotes, but not significantly as compared to controls (P=0.14). HPLC analysis showed that increased RLP-cholesterol level was not due to conventional VLDL-LDL size RLP, but to those in large HDL size in the homozygote. In heterozygotes, bimodal distribution of RLP-cholesterol level was found in lipoprotein sizes of conventional VLDL-LDL and large HDL. Subjects with CETP deficiency appeared to have low levels of TG response and diminished remnant lipoprotein formation after fat-load. (C) 2007 Elsevier Ireland Ltd. All rights reserved.