Goldberg I J, Le N A, Paterniti J R, Ginsberg H N, Lindgren F T, Brown W V
J Clin Invest. 1982 Dec;70(6):1184-92. doi: 10.1172/jci110717.
The role of the enzyme hepatic triglyceride lipase was investigated in a primate model, the cynomolgus monkey. Antisera produced against human postheparin hepatic lipase fully inhibited cynomolgus monkey posttheparin plasma hepatic triglyceride lipase activity. Lipoprotein lipase activity was not inhibited by this antisera. Hepatic triglyceride lipase activity in liver biopsies was decreased by 65-90% after intravenous infusion of this antisera into the cynomolgus monkey. After a 3-h infusion of the antisera, analytic ultracentrifugation revealed an increase in mass of very low density lipoproteins (S(f) 20-400). Very low density lipoprotein triglyceride isolated by isopycnic ultracentrifugation increased by 60-300%. Analytic ultracentrifugation revealed an increase in mass of lipoproteins with flotation greater than S(f) 9 (n = 4). The total mass of intermediate density lipoproteins (S(f) 12-20) approximately doubled during the 3 h of in vivo enzyme inhibition. While more rapidly floating low density lipoproteins (S(f) 9-12) increased, the total mass of low density lipoproteins decreased after infusion of the antibodies. The changes in high density lipoproteins did not differ from those in control experiments. In order to determine whether the increases of plasma concentrations of very low density lipoproteins were due to an increase in the rate of synthesis or a decrease in the rate of clearance of these particles, the metabolism of radiolabeled homologous very low density lipoproteins was studied during intravenous infusion of immunoglobulin G prepared from the antisera against hepatic triglyceride lipase (n = 3) or preimmune goat sera (n = 3). Studies performed in the same animals during saline infusion were used as controls for each immunoglobulin infusion. There was a twofold increase in the apparent half-life of the very low density lipoprotein apolipoprotein-B tracer in animals receiving the antibody, consistent with a decreased catabolism of very low density lipoproteins. Concomitantly, the rise in low density lipoprotein apoprotein-B specific activity was markedly delayed. None of these changes were observed during infusion of preimmune immunoglobulin G.Hepatic triglyceride lipase participates with lipoprotein lipase in the hydrolysis of the lipid in very low density lipoproteins, intermediate density lipoproteins, and the larger low density lipoproteins (S(f) 9-12). Thus, hepatic triglyceride lipase appears to function in a parallel role with lipoprotein lipase in the conversion of very low density and intermediate density lipoproteins to low density lipoproteins (S(f) 0-9).
在灵长类动物食蟹猴模型中研究了肝甘油三酯脂肪酶的作用。针对人肝素后肝脂肪酶产生的抗血清完全抑制了食蟹猴肝素后血浆肝甘油三酯脂肪酶活性。该抗血清未抑制脂蛋白脂肪酶活性。将这种抗血清静脉输注到食蟹猴体内后，肝活检中的肝甘油三酯脂肪酶活性降低了65% - 90%。输注抗血清3小时后，分析超速离心显示极低密度脂蛋白（S(f) 20 - 400）的质量增加。通过等密度超速离心分离的极低密度脂蛋白甘油三酯增加了60% - 300%。分析超速离心显示漂浮率大于S(f) 9的脂蛋白质量增加（n = 4）。在体内酶抑制的3小时内，中间密度脂蛋白（S(f) 12 - 20）的总质量大约增加了一倍。虽然漂浮更快的低密度脂蛋白（S(f) 9 - 12）增加，但输注抗体后低密度脂蛋白的总质量下降。高密度脂蛋白的变化与对照实验中的变化没有差异。为了确定极低密度脂蛋白血浆浓度升高是由于这些颗粒的合成速率增加还是清除速率降低，在静脉输注由抗肝甘油三酯脂肪酶的抗血清制备的免疫球蛋白G（n = 3）或免疫前山羊血清（n = 3）期间，研究了放射性标记的同源极低密度脂蛋白的代谢。在相同动物中进行的生理盐水输注期间的研究用作每次免疫球蛋白输注的对照。接受抗体的动物中极低密度脂蛋白载脂蛋白B示踪剂的表观半衰期增加了两倍，这与极低密度脂蛋白分解代谢降低一致。同时，低密度脂蛋白载脂蛋白B比活性的升高明显延迟。在输注免疫前免疫球蛋白G期间未观察到这些变化。肝甘油三酯脂肪酶与脂蛋白脂肪酶一起参与极低密度脂蛋白、中间密度脂蛋白和较大的低密度脂蛋白（S(f) 9 - 12）中脂质的水解。因此，肝甘油三酯脂肪酶在将极低密度脂蛋白和中间密度脂蛋白转化为低密度脂蛋白（S(f) 0 - 9）的过程中似乎与脂蛋白脂肪酶发挥平行作用。
