Genetics
CETP deficiency sharply blunts the post-meal triglyceride spike and remnant lipoprotein formation (Atherosclerosis 2008)
Original title: Decreased post-prandial triglyceride response and diminished remnant lipoprotein formation in cholesteryl ester transfer protein (CETP) deficiency
Since CETP deficiency produces a low-LDL, high-HDL phenotype including apoE-rich large HDL that could accelerate remnant lipoprotein uptake in the liver during the post-prandial state, this study measured plasma remnant-like lipoprotein particle (RLP) levels after an oral fat load in one homozygous and three heterozygous CETP-deficient subjects compared to apoE3/3 controls. The area under the curve for triglyceride levels was remarkably decreased in CETP deficiency compared to controls (423 vs 926 mg/dL times h in heterozygotes and controls, P=0.012), with the homozygote also showing a low triglyceride AUC (416 mg/dL times h). Plasma RLP-cholesterol was decreased in heterozygotes, though not significantly (P=0.14). HPLC analysis showed that in the homozygote, increased RLP-cholesterol occurred in large-HDL-sized particles rather than conventional VLDL-LDL-sized particles, with heterozygotes showing a bimodal distribution across both size ranges. The authors conclude CETP deficiency is associated with a blunted post-prandial triglyceride response and diminished remnant lipoprotein formation.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.