DEFECT IN AN INTRAHEPATIC DEGRADATION OF APOLIPOPROTEIN-B IN SUNCUS -AN ANIMAL-MODEL OF HYPOBETALIPOPROTEINEMIA

We have previously shown that fatty liver is easily induced in suncus by starvation and that the plasma level of apolipoprotein B (ape B) is very low, We also found that hepatic acyl coenzyme A cholesterol acyl transferase (ACAT) activity is almost absent in the animals, resulting in decreased cholesteryl ester contents in the liver, A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the d efect in the assembly process of apo B-containing lipoproteins, leadin g to a low level of plasma apo B, Another possible explanation for the induction of fatty liver in suncus is a defect in apo B-processing in the liver, In this study, we investigated the hepatic synthetic rate and intrahepatic degradation of apo B using primary cultured hepatocyt es derived fi om suncus and rats, In order to estimate intrahepatic de gradation of apo B, we added N-acetylleucylleucynorleucinal to the cul ture medium as an inhibitor of apo B degradation, The basal synthesis of apo B in suncus hepatocytes was 50% of that in rat, Intracellular d egradation of apo B was not observed in suncus hepatocytes, while it w as obvious in rat hepatocytes, This evidence suggests that the lower s ecretion rate of apo B-lipoprotein is not due to the intrahepatic degr adation of apo B, but may be due to the low synthetic rate of apo B.