ABSTRACT
We have previously shown that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apoB) was very low. We also previously reported that a defect in the assembling process of apo B-containing lipoprotein (very low density lipoprotein, 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 also found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is very low 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 defect in the assembling process of VLDL. In this study, we investigated the effect of cholesterol-feeding, which induces an increase in triglyceride and cholesteryl ester of the liver as a consequence of the induction of both intestinal and hepatic ACAT activities, on the secretion of VLDL. Although the basal ACAT activity of intestinal mucosa was high, cholesterol-feeding did not induce either an increase in plasma lipid or an increase in intestinal ACAT activities in suncus. The hepatic secretion rate of VLDL was estimated by treatment with Triton WR1339, which is well known to inhibit the catabolism of VLDL. Cholesterol-feeding caused a slight increase in hepatic triglyceride and cholesteryl ester but no increase either in the secretion rate of VLDL or in hepatic ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Apolipoproteins B/metabolism , Liver/metabolism , Sterol O-Acyltransferase/metabolism , Animals , Cholesterol/administration & dosage , Cholesterol/blood , In Vitro Techniques , Intestinal Mucosa/enzymology , Lipoproteins, VLDL/blood , Lipoproteins, VLDL/metabolism , Liver/enzymology , Male , Protein Processing, Post-Translational , ShrewsABSTRACT
We previously showed that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apo B) was very low. There are three possible explanations for the low level of apo B in the animals: low synthetic rate, low secretion rate, and rapid catabolism in the circulation of apo B. We measured post-heparin lipolytic activity (lipoprotein lipase activity), which plays a key role in the catabolism of apo B-containing lipoprotein, VLDL, and found no difference between rats and suncus. We also investigated the hepatic synthetic rate of apo B by liver perfusion studies. Newly synthesized apo B in the suncus liver was detected by immunoprecipitation and found to amount to 12.5% of that in rats. The secretion rate of VLDL in suncus, which was estimated by intravenous injection of Triton WR1339, was 13.8% of that in rats. These two results suggest that there is no major defect in the secretory process. We separated Golgi apparatus from rat and suncus livers, and found much fewer lipoprotein particles in suncus than in rat Golgi apparatus. This evidence suggests that there is no defect in the lipolytic process or hepatic secretory process of apo B-containing lipoprotein, VLDL, but there may be a defect in the assembly process of VLDL and/or in the synthetic process of apo B in suncus. Such a defect may be one of the reasons for starvation-induced fatty liver in suncus.
Subject(s)
Fatty Liver/metabolism , Fatty Liver/physiopathology , Lipoproteins, VLDL/biosynthesis , Lipoproteins, VLDL/metabolism , Liver/metabolism , Animals , Apolipoproteins B/biosynthesis , Apolipoproteins B/blood , Chromatography, High Pressure Liquid , Disease Models, Animal , Fasting/metabolism , Heparin/pharmacology , Lipoprotein Lipase/metabolism , Lipoproteins, LDL/analysis , Lipoproteins, VLDL/blood , Male , Rats , Rats, Wistar , Secretory Rate , ShrewsABSTRACT
We reported previously that apolipoprotein B is not actively secreted from suncus liver. In the present study we have investigated the hepatic cholesterol metabolism, which plays a critical role in the secretion of apo B. We found that the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in suncus liver is high and that acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity is almost absent in contrast to rats. As a result, the hepatic content of cholesterol ester, upon which apoprotein B secretion partly depends, is very low in suncus. The deficiency of ACAT activity may cause the defect in active secretion of apoprotein B-containing lipoproteins in suncus.
Subject(s)
Arvicolinae/metabolism , Liver/enzymology , Rats, Wistar/metabolism , Sterol O-Acyltransferase/deficiency , Animals , Hydroxymethylglutaryl CoA Reductases/metabolism , Male , RatsABSTRACT
alpha 1-antitrypsin (alpha 1-AT) is a glycoprotein called an acute phase reactant, which increases in blood in a variety of inflammations. alpha 1-AT deficiency with an inherited remarkable reduction of alpha 1-AT in blood has two major disorders, pulmonary emphysema and liver diseases, particularly an infantile cirrhosis. It is of great interest that each disorder has peculiar mechanisms based on an imbalance between proteases and protease inhibitors. alpha 1-AT constitutes genetic polymorphism of which alpha 1-AT deficiency presents rare PiZ or PiZ-like variants. alpha 1-AT deficiency is an inherited metabolic disorder associated with not only a severe reduction of alpha 1-AT in blood, but also amino acid substitutions of alpha 1-AT due to gene variations.
