Defect in assembly process of very-low-density lipoprotein in suncus liver: an animal model of fatty liver.
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.
Nagayoshi
A
A
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo.
Matsuki
N
N
Saito
H
H
Tsukamoto
K
K
Kaneko
K
K
Wakashima
M
M
Kinoshita
M
M
Yamanaka
M
M
Teramoto
T
T
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005215:Fasting / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism* / Q000503:physiopathology*; D006493:Heparin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000032:analysis; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate; D012788:Shrews
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D006493:Heparin; D008071:Lipoprotein Lipase