A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism
A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism
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DOI：
10.1074/jbc.274.27.19055
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发表时间：
1999-07-02
影响因子：
4.8
通讯作者：
Silverstein, RL
中科院分区：
文献类型：
--
作者：
Febbraio, M;Abumrad, NA;Silverstein, RL
通过定向同源重组在小鼠体内产生清道夫受体基因 CD36 的无效突变。这些小鼠没有产生可检测到的 CD36 蛋白，可以正常繁殖。与对照小鼠相比，无效小鼠腹膜巨噬细胞中氧化低密度脂蛋白的结合和摄取显着减少。 CD36缺失动物的空腹胆固醇、非酯化游离脂肪酸和三酰基甘油水平显着增加。胆固醇的增加主要在高密度脂蛋白部分，而三酰甘油的增加在极低密度脂蛋白部分。与野生型对照相比，无效动物的空腹血糖水平较低。无效小鼠的脂肪细胞对 H-3 标记的油酸的摄取显着减少。然而，下降仅限于脂肪酸：牛血清白蛋白的低比例，这表明 CD36 对于摄取过程的高亲和力成分是必需的。这些数据为 CD36 在脂蛋白/脂肪酸代谢中的功能性作用提供了证据，而这一作用以前未被充分认识。
A null mutation in the scavenger receptor gene CD36 was created in mice by targeted homologous recombination. These mice produced no detectable CD36 protein, were viable, and bred normally. A significant decrease in binding and uptake of oxidized low density lipoprotein was observed in peritoneal macrophages of null mice as compared with those from control mice. CD36 null animals had a significant increase in fasting levels of cholesterol, nonesterified free fatty acids, and triacylglycerol. The increase in cholesterol was mainly within the high density lipoprotein fraction, while the increase in triacylglycerol was within the very low density lipoprotein fraction. Null animals had lower fasting serum glucose levels when compared with wild type controls. Uptake of H-3-labeled oleate was significantly reduced in adipocytes from null mice. However, the decrease was limited to the low ratios of fatty acid:bovine serum albumin, suggesting that CD36 was necessary for the high affinity component of the uptake process. The data provide evidence for a functional role for CD36 in lipoprotein/fatty acid metabolism that was previously underappreciated.