Effects of a thyromimetic on apolipoprotein B-100 in rats

We have studied the effects of a cardiac sparing thyromimetic, CGS 23425, o n postprandial levels of triglycerides, abundance of apolipoprotein B (apo B) protein and hepatic apo B mRNA expression in rats. When compared with co ntrol rats, triglyceride clearance was significantly accelerated by treatme nt with CGS 23425. A full return to baseline values was achieved within 8 h after ingesting a large quantity of fat, as compared to >24h in control an imals. The abundance of apo B-100 protein in CGS 23425-treated hyperlipidem ic rats decreased in a dose-dependent manner, but levels of apo B-48 were n ot significantly affected. Like L-triiodothyronine (L-T-3), treatment with 30 mug/kg CGS 23425 for 6 or 9 days decreased the levels of apo B-100 prote in by 80% and 40% respectively. This change was paralleled by a 27% reducti on in hepatic apo B-100 mRNA. To investigate a potential mechanism of CGS 2 3425 action, we measured in vitro apo B mRNA editing activity in hepatocell ular extract from control or CGS 23425-treated rats. Treatment with CGS 234 25 increased activity of the hepatic apo B-100 editosome, apobec-1. In huma n hepatoma cells which lack apobec-1 activity, apo B-100 mRNA levels remain ed the same in cells treated with or without the agent. In summary, these o bservations show that CGS 23425 decreases the levels of apo B-100 in rats. This action of CGS 23425 involves apo B-100 mRNA editing activity.