Goldberg I J, Le N A, Ginsberg H N, Krauss R M, Lindgren F T
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
J Clin Invest. 1988 Feb;81(2):561-8. doi: 10.1172/JCI113354.
To clarify the role of lipoprotein lipase (LPL) in the catabolism of nascent and circulating very low density lipoproteins (VLDL) and in the conversion of VLDL to low density lipoproteins (LDL), studies were performed in which LPL activity was inhibited in the cynomolgus monkey by intravenous infusion of inhibitory polyclonal or monoclonal antibodies. Inhibition of LPL activity resulted in a three- to fivefold increase in plasma triglyceride levels within 3 h. Analytical ultracentrifugation and gradient gel electrophoresis demonstrated an increase predominantly in more buoyant, larger VLDL (Sf 400-60). LDL and high density lipoprotein (HDL) cholesterol levels fell during this same time period, whereas triglyceride in LDL and HDL increased. Kinetic studies, utilizing radiolabeled human VLDL, demonstrated that LPL inhibition resulted in a marked decrease in the catabolism of large (Sf 400-100) VLDL apolipoprotein B (apoB). The catabolism of more dense VLDL (Sf 60-20) was also inhibited, although to a lesser extent. However, there was a complete block in the conversion of tracer in both Sf 400-100 and 60-20 VLDL apoB into LDL during LPL inhibition. Similarly, endogenous labeling of VLDL using [3H]leucine demonstrated that in the absence of LPL, no radiolabeled apoB appeared in LDL. We conclude that although catabolism of dense VLDL continues in the absence of LPL, this enzyme is required for the generation of LDL.
为阐明脂蛋白脂肪酶（LPL）在新生和循环极低密度脂蛋白（VLDL）分解代谢以及VLDL转化为低密度脂蛋白（LDL）过程中的作用，我们进行了相关研究，通过静脉输注抑制性多克隆或单克隆抗体来抑制食蟹猴体内的LPL活性。LPL活性受到抑制后，3小时内血浆甘油三酯水平增加了三到五倍。分析超速离心和梯度凝胶电泳表明，主要是更漂浮、更大的VLDL（Sf 400 - 60）增加。在此期间，LDL和高密度脂蛋白（HDL）胆固醇水平下降，而LDL和HDL中的甘油三酯增加。利用放射性标记的人VLDL进行的动力学研究表明，LPL抑制导致大的（Sf 400 - 100）VLDL载脂蛋白B（apoB）分解代谢显著减少。密度更高的VLDL（Sf 60 - 20）的分解代谢也受到抑制，尽管程度较小。然而，在LPL抑制期间，Sf 400 - 100和60 - 20 VLDL apoB中的示踪剂向LDL的转化完全受阻。同样，使用[3H]亮氨酸对VLDL进行内源性标记表明，在没有LPL的情况下，LDL中未出现放射性标记的apoB。我们得出结论，虽然在没有LPL的情况下高密度VLDL的分解代谢仍在继续，但生成LDL需要这种酶。
