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Journal of Lipid Research, Vol. 50, 999-1011, May 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Chylomicron remnants are increased in the postprandial state in CD36 deficiency

Daisaku Masuda^1,*, Ken-ichi Hirano, Hiroyuki Oku, Jose C. Sandoval, Ryota Kawase, Miyako Yuasa-Kawase, Yasushi Yamashita^**, Masanori Takada, Kazumi Tsubakio-Yamamoto, Yoshihiro Tochino^*, Masahiro Koseki, Fumihiko Matsuura, Makoto Nishida, Toshiharu Kawamoto^**, Masato Ishigami, Masatsugu Hori, Iichiro Shimomura^* and Shizuya Yamashita

^* Departments of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Department of Biomedical Informatics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Department of Cardiology, Kawasaki Hospital, 3-3-1 Higashiyama-cho, Hyogo Ward, Kobe, Hyogo 652-0042, Japan
^** Department of Cardiology, Kure Heart Center, National Hospital Organization Kure Medical Center, 3-1 Aoyama-cho, Kure, Hiroshima 737-0023, Japan
Health Care Center, Osaka University, 1-7 Machikaneyama, Toyonaka, Osaka 560-0043, Japan

This work was supported by the following grants: a grant-in-aid for Scientific Research (No. 18659267) to S. Yamashita from the Ministry of Education, Science, Sports and Culture in Japan; a grant from Mitsui Life Social Welfare Foundation to S. Yamashita; a grant from Takeda Science Foundation to S. Yamashita; and an Osaka Heart Club Grant for Cardiovascular Disease to D. Masuda.

Published, JLR Papers in Press, August 27, 2008.

¹ To whom correspondence should be addressed. e-mail: masuda{at}imed2.med.osaka-u.ac.jp

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.

Supplementary key words atherosclerosis • apolipoprotein B-48 • free fatty acids • free glycerol • TG-rich lipoproteins • small dense LDL

Abbreviations: apoB-48, apolipoprotein B-48; CM, chylomicron; FABP, fatty acid binding protein; FFA, free fatty acid; LCFA, long-chain fatty acid; LPL, lipoprotein lipase; MetS, metabolic syndrome; OFL, oral fat loading; TC, total cholesterol; TG, triglyceride; PL, phospholipids; RLP, remnant lipoprotein particle; sdLDL, small dense LDL; TRL, triglyceride-rich lipoprotein; WT, wild-type

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