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.
Inazu
Akihiro
A
Department of Laboratory Science, Graduate School of Medical Science, Kanazawa University, Kodatsuno 5-11-80, Kanazawa, Ishikawa 920-0942, Japan. inazua@mhs.mp.kanazawa-u.ac.jp
Nakajima
Katsuyuki
K
Nakano
Takamitsu
T
Niimi
Manabu
M
Kawashiri
Masa-aki
MA
Nohara
Atsushi
A
Kobayashi
Junji
J
Mabuchi
Hiroshi
H
D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics; D002784:Cholesterol / Q000096:biosynthesis*; D053480:Cholesterol Ester Transfer Proteins / Q000172:deficiency*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood*
D001057:Apolipoproteins E; D053480:Cholesterol Ester Transfer Proteins; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol