Briand F, Bailhache E, Nguyen P, Krempf M, Magot T, Ouguerram K
Diabetes Obes Metab. 2007 Jan;9(1):139-42. doi: 10.1111/j.1463-1326.2006.00588.x.
In reverse cholesterol transport (RCT), hepatic Scavenger Receptor class B type I (SR-BI) plays an important role by mediating the selective uptake of high-density lipoprotein cholesteryl ester (HDL-CE). However, little is known about this antiatherogenic mechanism in insulin resistance. HDL-CE selective uptake represents the main process for HDL-CE turnover in dog, a species lacking cholesteryl ester transfer protein activity. We therefore investigate the effects of diet induced insulin resistance on RCT.
Five beagle dogs, in healthy and insulin resistant states, underwent a primed constant infusion of [1,2(13)C(2)]acetate and [5,5,5-(2)H(3)]leucine, as labelled precursors of CE and apolipoprotein (apo) A-I, respectively. Data were analysed using modelling methods.
HDL-apo A-I concentration did not change in insulin resistant state but apo A-I absolute production rate (APR) and fractional catabolic rate (FCR) were both higher (2.2- and 2.4-fold, respectively, p < 0.05). HDL-CE levels were lower (1.2-fold, p < 0.05). HDL-CE APR and FCR were both lower (2.3- and 2-fold, respectively, p < 0.05), as well as selective uptake (2.6-fold, p < 0.05).
Lower HDL-CE selective uptake suggests that RCT is impaired in obese insulin resistant dog.
在逆向胆固醇转运（RCT）过程中，肝脏I型清道夫受体（SR-BI）通过介导高密度脂蛋白胆固醇酯（HDL-CE）的选择性摄取发挥重要作用。然而，关于胰岛素抵抗中这种抗动脉粥样硬化机制的了解甚少。HDL-CE选择性摄取是犬类HDL-CE周转的主要过程，犬类缺乏胆固醇酯转运蛋白活性。因此，我们研究了饮食诱导的胰岛素抵抗对RCT的影响。
五只处于健康和胰岛素抵抗状态的比格犬，分别接受[1,2(13)C(2)]乙酸盐和[5,5,5-(2)H(3)]亮氨酸的首剂量恒速输注，分别作为CE和载脂蛋白（apo）A-I的标记前体。使用建模方法分析数据。
在胰岛素抵抗状态下，HDL-apo A-I浓度未发生变化，但apo A-I绝对生成率（APR）和分数分解代谢率（FCR）均更高（分别为2.2倍和2.4倍，p<0.05）。HDL-CE水平较低（1.2倍，p<0.05）。HDL-CE的APR和FCR均较低（分别为2.3倍和2倍，p<0.05），以及选择性摄取（2.6倍，p<0.05）。
HDL-CE选择性摄取降低表明肥胖胰岛素抵抗犬的RCT受损。
