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© 2003 by the American Diabetes Association, Inc.
Letters: Observations |
Lipoprotein Abnormalities in Human Genetic CD36 Deficiency Associated With Insulin Resistance and Abnormal Fatty Acid Metabolism
1 Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan
2 Department of Molecular Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
CD36 is an 88-kDa membranous protein with multiple relevant function that is widely expressed in human tissues (1). Because we and others (2) found human genetic deficiency of this molecule, we have elucidated the molecular bases and pathophysiology. We have reported that the human deficiency may be associated with insulin resistance (3) and abnormal dynamics of long-chain fatty acid (LCFA) (4). The aim of the present study was to further characterize lipid and lipoprotein metabolism in the human genetic CD36 deficiency, especially focusing on postprandial responses.
Seven Japanese patients with type I CD36 deficiency (cases 1–7) were subjected. They were divided into the following two groups: group A, two younger patients we have recently identified (cases 1 and 2); and group B, patients >50 years of age (cases 3–7, reported in our previous paper [3]). For the analysis of each group, aged-matched healthy and nonobese volunteers were subjected as control subjects (Table 1). First, we confirmed that insulin resistance was also present in the two younger patients (group A).
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At the fasting state, "midbands," which imply the accumulation of remnant lipoproteins, were observed in group B but not in group A. Preparative ultracentrifugation confirmed an increase in intermediate-density lipoprotein cholesterol in the all of the CD36-deficient subjects in group B compared with the control subjects. The oral fat loading test demonstrated that the patients in group B presented postprandial hyperlipidemia with the accumulation of small intestine-derived lipids. Whereas the patients in group A did not show apparent abnormalities, though they did have insulin resistance.
The present study indicated that this monogenic disorder with the abnormal metabolism in LCFA and insulin resistance may cause the phenotypic expression of hyperlipidemia at both fasting and postprandial states. These data also suggest that the clinical manifestation is affected by the acquired factors, such as aging and dietary contents. We believe that human genetic CD36 deficiency may be a monogenic form of "metabolic syndrome." Further studies to elucidate molecular mechanism for the phenotypic expression in CD36-deficient states are under way in our laboratories.
Acknowledgments
This work was supported by grants-in-aid to K.H. (no. 13671191) and S.Y. (nos. 11557055 and 10671070) from the Ministry of Education, Science, Sports, and Culture of Japan.
We gratefully thank Natsu Iwamoto, Sonoe Shima, and Atsuko Ohya for the skillful technical assistance.
Footnotes
Address correspondence to Ken-ichi Hirano, MD, PhD, Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: khirano{at}kb3.so-net.ne.jp.
References
- Febbraio M, Hajjar DP, Silverstein RL: CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest 108:785–791, 2001[Medline]
- Yamamoto N, Ikeda H, Tandon NN, Herman J, Tomiyama Y, Mitani T, Sekiguchi S, Lipsky R, Kralisz U, Jamieson GA: A platelet membrane glycoprotein (GP) deficiency in healthy blood donors: Naka, platelet lack detectable GP IV(CD36). Blood 76:1698–1703, 1990
[Abstract/Free Full Text]
- Miyaoka K, Kuwasako T, Hirano K, Nozaki S, Yamashita S, Matsuzawa Y: CD36 deficiency associated with insulin resistance. Lancet 357:686–687, 2001[Medline]
- Yoshizumi T, Nozaki S, Fukuchi K, Yamasaki K, Fukuchi T, Maruyama T, Tomiyama Y, Yamashita S, Nishimura T, Matsuzawa Y: Pharmacokinetics and metabolism of iodine-123-BMIPP fatty acid analogue in normal and CD36-deficient subjects. J Nucl Med 41:1134–1138, 2000
[Abstract/Free Full Text]
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