Chylomicron remnants are increased in the postprandial state in CD36 deficiency
Chylomicron remnants are increased in the postprandial state in CD36 deficiency
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DOI：
10.1194/jlr.p700032-jlr200
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发表时间：
2009-05-01
影响因子：
6.5
通讯作者：
Yamashita, Shizuya
中科院分区：
文献类型：
--
作者：
Masuda, Daisaku;Hirano, Ken-ichi;Yamashita, Shizuya
包括血脂异常、高血糖症和高血压在内的危险因素的聚集是高度致动脉粥样硬化的，沿着来自富含甘油三酯（TG）的脂蛋白的过量残余物。CD 36参与肌肉和小肠中长链脂肪酸（LCFA）的摄取。CD 36缺陷（CD 36-D）患者存在餐后高血糖、胰岛素抵抗和高血压。为了研究CD 36-D餐后高脂血症的潜在机制，我们分析了口服脂肪负荷（OFL）后CD 36-D患者和CD 36敲除（CD 36-KO）小鼠的脂蛋白谱。在CD 36-D患者中，OFL后血浆甘油三酯、载脂蛋白B-48（apoB-48）、游离脂肪酸（FFA）和游离甘油水平远高于对照组，沿着乳糜微粒（CM）残留物和小而密的低密度脂蛋白（sdLDL）颗粒的增加。在CD 36-KO小鼠中，OFL后血浆和肠淋巴液中小于CM的脂蛋白显著增加，参与FFA生物合成的基因，如脂肪酸结合蛋白（FABP）-1和FAS的mRNA水平显著增加。这些结果表明，CD 36-D可能通过增加CM残余物的血浆水平而增加动脉粥样硬化风险，这是由于肠中尺寸小于CM的脂蛋白的合成增加。增田，D.，K.平野，H。Oku，J. C.桑多瓦尔河Kawase，M. Yuasa-Kawase，Y.山下，M。高田，加-地Tsubakio-Yamamoto，Y.托奇诺湾Koseki，F. Matsuura，M. Nishida，T. Kawamoto，M. Ishigami，M.霍里岛Shimomura和S.山下CD 36缺乏者餐后乳糜微粒残留增加。J. Lipid Res. 2009. 50：999-1011。
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. jlr 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, D., K. Hirano, H. Oku, J. C. Sandoval, R. Kawase, M. Yuasa-Kawase, Y. Yamashita, M. Takada, K. Tsubakio-Yamamoto, Y. Tochino, M. Koseki, F. Matsuura, M. Nishida, T. Kawamoto, M. Ishigami, M. Hori, I. Shimomura, and S. Yamashita. Chylomicron remnants are increased in the postprandial state in CD36 deficiency. J. Lipid Res. 2009. 50: 999-1011.