Welty Francine K, Lichtenstein Alice H, Barrett P Hugh R, Dolnikowski Gregory G, Schaefer Ernst J
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center at Tufts University, 711 Washington St, Boston, MA 02111, USA.
Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1703-7. doi: 10.1161/01.ATV.0000137975.14996.df. Epub 2004 Jul 8.
Our purpose was to determine the relationship between apolipoprotein (apo) A-I and apoB-48 and apoB-100 metabolism in moderately hypercholesterolemic humans.
The kinetics of apoA-I within high-density lipoprotein (HDL), apoB-48 and apoB-100 within triglyceride-rich lipoproteins, and apoB-100 within intermediate-density lipoprotein and low density-lipoprotein (LDL) were examined with a primed constant infusion of [5,5,5-(2)H(3)] leucine in the fed state (hourly feeding) in 23 subjects after consumption of a 36% total fat diet. Lipoproteins were isolated by ultracentrifugation; apolipoproteins by SDS-PAGE gels; and isotope enrichment assessed by gas chromatograph/mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data with SAAM II. ApoA-I production rate (PR) was correlated with LDL apoB-100 pool size (PS; r=0.49; P=0.017) and LDL cholesterol (r=0.61; P=0.002), whereas apoA-I fractional catabolic rate (FCR) was inversely correlated with apoB-48 FCR (r=-0.40; P=0.05) but not with very low-density lipoprotein apoB-100 FCR.
Two links exist between apoA-I and apoB kinetics: 1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and 2) delayed chylomicron remnant clearance (represented by apoB-48 FCR) is associated with enhanced apoA-I FCR, a finding indicating that alterations in intestinal lipoproteins may be more important in determining HDL cholesterol levels than changes in liver lipoproteins. Using stable isotopes in humans, 2 links were observed between apoA-I and apoB kinetics: (1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and (2) delayed chylomicron remnant clearance is associated with enhanced apoA-I FCR, indicating that alterations in intestinal lipoproteins may be more important in determining HDL-C levels than changes in liver lipoprotein particles.
我们的目的是确定中度高胆固醇血症患者中载脂蛋白（apo）A-I与apoB-48和apoB-100代谢之间的关系。
在23名受试者摄入含36%总脂肪的饮食后处于进食状态（定时喂食）时，通过[5,5,5-(2)H(3)]亮氨酸的首剂恒速输注，检测高密度脂蛋白（HDL）中的apoA-I、富含甘油三酯脂蛋白中的apoB-48和apoB-100以及中密度脂蛋白和低密度脂蛋白（LDL）中的apoB-100的动力学。通过超速离心分离脂蛋白；通过SDS-PAGE凝胶分离载脂蛋白；通过气相色谱/质谱法评估同位素富集情况。使用SAAM II对数据进行多室建模计算动力学参数。apoA-I生成率（PR）与LDL apoB-100池大小（PS；r = 0.49；P = 0.017）和LDL胆固醇（r = 0.61；P = 0.002）相关，而apoA-I分解代谢率（FCR）与apoB-48 FCR呈负相关（r = -0.40；P = 0.05），但与极低密度脂蛋白apoB-100 FCR无关。
apoA-I与apoB动力学之间存在两个联系：1）当LDL apoB-100 PS较高时，apoA-I PR增加；2）乳糜微粒残粒清除延迟（以apoB-48 FCR表示）与apoA-I FCR增强相关，这一发现表明肠道脂蛋白的改变在决定HDL胆固醇水平方面可能比肝脏脂蛋白的变化更重要。在人体中使用稳定同位素，观察到apoA-I与apoB动力学之间存在两个联系：（1）当LDL apoB-100 PS较高时，apoA-I PR增加；（2）乳糜微粒残粒清除延迟与apoA-I FCR增强相关，表明肠道脂蛋白的改变在决定HDL-C水平方面可能比肝脏脂蛋白颗粒的变化更重要。
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