|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
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
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