LIPID TRANSPORT SYSTEM IN THE LIVER

我们以前的研究表明，饥饿很容易诱发梭子鱼脂肪肝，而且梭子鱼血浆载脂蛋白B（apo B）水平很低。我们以前也报道过，含载脂蛋白B的脂蛋白（极低密度脂蛋白，VLDL）的组装过程中的缺陷可能是导致血浆载脂蛋白B水平低和饥饿诱导脂肪肝的原因之一。我们发现，肝酰基辅酶A胆固醇酰基转移酶（ACAT）的活性几乎是不存在的动物，导致在肝脏中的胆固醇酯酶减少。结论：在正常人肝脏中，胆固醇酯的缺乏可能是载脂蛋白B组装过程缺陷的原因之一。另一种可能性是肝脏中载脂蛋白B合成缺陷，导致低β脂蛋白血症和脂肪肝。我们用原代培养的肝细胞研究了载脂蛋白B的肝合成率和载脂蛋白B的肝内降解。 ...更多信息 用apo B降解抑制剂N-乙酰亮氨酰亮氨正亮氨酸（N-acetylleucynorleucinal）测定了载脂蛋白B（apo B）在肝内的降解。松垂中apo B的合成为大鼠的14%~ 29%。载脂蛋白B在大鼠肝细胞中有明显降解，而在向日葵肝细胞中未见降解。这一结果提示，梭子鱼apo B-脂蛋白分泌率低不是由于apo B在肝内降解增强所致，而可能是由于apo B在梭子鱼体内合成率低所致。VLDL组装缺陷的另一种可能性是微粒体甘油三酯转移蛋白的低活性，据报道，该蛋白在无β脂蛋白血症中缺乏。并测定了其在小肠粘膜和肝脏中的活性。小肠粘膜中的活性与大鼠的活性基本相同，肝脏中的活性约为大鼠的30%。饥饿12小时后，酶活性无明显变化。然而，当破碎的动物被重新喂食时，活性显著增强。总之，饥饿引起的脂肪肝可能与ACAT活性降低、apo B合成降低和MTP活性降低有关，提示这些因素在VLDL的合成中起关键作用。少

We have previously shown that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apo B) was very low. We also previously reported that a defect in the assembling process of apo B-containing lipoprotein (very low density lipoprptein, VLDL) may be one of the reasons for the low level of plasma apo B and for induction of fatty liver by starvation in suncus. We found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is almost absent in the animals, resulting in decreased cholesteryl ester conteints in the liver. A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the defect in the assembling process of apo B-containing lipoproteins. Another possibility is a defect in apo B-synthesis in the liver, resulting in hypobetalipoproteinemia and in fatty liver. We investigated the hepatic syntetic rate of apo B and intrahepatic degradation of apo B using primary cultures of hepatocytes derived from … More suncus and rats, and using N-acetylleucylleucynorleucinal, an inhibitor of apo B degradation we estimated the intrahepatic degradation of apo B.In order to compare the apo B syntesis of suncus with that of rat, we estimated it as the ratio of apo B syntesis over albumin which were newly syntesized in hepatocytes. The apo B syntesis in suncus was between 14% and 29% of that in rat. Intracellular degradation of apolipoprotein B was not observed in suncus hepatocytes, while it was obvious in rat hepatocytes. This evidence suggests that the low secretion rate of apo B-lipoprotein in suncus was not resulted from enhanced intrahepatic degradation of apo B but may be from low syntetic rate of apo B in suncus. Another possibility of the defect of VLDL-assembly is low activity of microsomal triglyceride transfer protein, which has been reported to be deficient in abetalipoproteinemia. We assayd the activity in suncus liver and intestinal mucosa. While the activity in suncus intestinal mucosa was almost same as that of rat, it was about 30% of rat in the liver. When suncus were starved for 12 hours, the activity was not changed. However, when the staved animals were refed, the activity was enhanced significantly. The evidence is compatible with rapid recovery from fatty liver when the animals were refed.In conclusion, fatty liver observed by starvation may be resulted from low ACAT activity, low apo B synthesis, and low MTP activity, suggesting that these factors play a key role in VLDL-assembling. Less