LIPID TRANSPORT SYSTEM IN THE LIVER

我们以前已经证明，饥饿容易诱发Suncus的脂肪肝，而且血浆载脂蛋白B(Apo B)水平很低。我们以前也报道过，含有载脂蛋白B的脂蛋白(极低密度脂蛋白，VLDL)组装过程中的缺陷可能是导致血浆载脂蛋白B水平低以及饥饿诱导海豚脂肪肝的原因之一。我们发现，在动物体内，肝脏酰基辅酶A胆固醇酰基转移酶(ACAT)活性几乎缺失，导致肝脏中胆固醇酯含量降低。Suncus肝脏胆固醇酯缺乏可能是载脂蛋白B组装过程缺陷的原因之一。另一种可能是肝脏载脂蛋白B合成缺陷，导致低β-脂蛋白血症和脂肪肝。我们利用…来源的肝细胞的原代培养研究了载脂蛋白B的肝脏联结率和肝内载脂蛋白B的降解。利用载脂蛋白B降解的抑制剂N-乙酰亮氨酸，我们估算了载脂蛋白B在肝内的降解。为了比较载脂蛋白B与大鼠的载脂蛋白B的合成，我们用肝细胞中新合成的载脂蛋白B与白蛋白的比值来估算载脂蛋白B的合成。Suncus的载脂蛋白B合成量是大鼠的14%~29%。Suncus肝细胞内未见载脂蛋白B的降解，而大鼠肝细胞内有明显的载脂蛋白B降解。这一证据表明，Suncus内载脂蛋白B的低分泌速率不是由于apo B在肝内降解的增强所致，而可能是由于Suncus内apo B的低突触速率所致。另一种VLDL组装缺陷的可能性是微粒体甘油三酯转运蛋白活性低，据报道，该蛋白在脂蛋白血症中缺乏。我们检测了Suncus肝脏和肠粘膜中的活性。Suncus肠粘膜中的活性与大鼠基本相同，肝脏中的活性约为大鼠的30%。当Suncus饥饿12小时时，这种活动没有改变。然而，当被隔离的动物被重新喂养时，其活性显著增强。结论：饥饿引起的脂肪肝可能是由于ACAT活性低、载脂蛋白B合成低和MTP活性低所致，提示这些因素在极低密度脂蛋白的形成中起关键作用。较少

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