Chylomicron remnants are increased in the postprandial state in CD36 deficiency.
The clustering of risk factors including dyslipidemia, hyperglycemia, and hypertension is highly atherogenic along with the excess of remnants from triglyceride (TG)-rich lipoproteins. CD36 is involved in the uptake of long-chain fatty acids (LCFAs) in muscles and small intestines. Patients with CD36 deficiency (CD36-D) have postprandial hypertriglyceridemia, insulin resistance, and hypertension. To investigate the underlying mechanism of postprandial hypertriglyceridemia in CD36-D, we analyzed lipoprotein profiles of CD36-D patients and CD36-knockout (CD36-KO) mice after oral fat loading (OFL). In CD36-D patients, plasma triglycerides, apolipoprotein B-48 (apoB-48), free fatty acids (FFAs), and free glycerol levels were much higher after OFL than those of controls, along with increases in chylomicron (CM) remnants and small dense low-density lipoprotein (sdLDL) particles. In CD36-KO mice, lipoproteins smaller than CM in size in plasma and intestinal lymph were markedly increased after OFL and mRNA levels of genes involved in FFA biosynthesis, such as fatty acid binding protein (FABP)-1 and FAS, were significantly increased. These results suggest that CD36-D might increase atherosclerotic risk by enhancing plasma level of CM remnants due to the increased synthesis of lipoproteins smaller than CM in size in the intestine.
Masuda
Daisaku
D
Departments of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hirano
Ken-ichi
K
Oku
Hiroyuki
H
Sandoval
Jose C
JC
Kawase
Ryota
R
Yuasa-Kawase
Miyako
M
Yamashita
Yasushi
Y
Takada
Masanori
M
Tsubakio-Yamamoto
Kazumi
K
Tochino
Yoshihiro
Y
Koseki
Masahiro
M
Matsuura
Fumihiko
F
Nishida
Makoto
M
Kawamoto
Toshiharu
T
Ishigami
Masato
M
Hori
Masatsugu
M
Shimomura
Iichiro
I
Yamashita
Shizuya
S