Effects of a thyromimetic on apolipoprotein B-100 in rats

Abstract

We have studied the effects of a cardiac sparing thyromimetic, CGS 23425, on postprandial levels of triglycerides, abundance of apolipoprotein B (apo B) protein and hepatic apo B mRNA expression in rats. When compared with control rats, triglyceride clearance was significantly accelerated by treatment with CGS 23425. A full return to baseline values was achieved within 8 h after ingesting a large quantity of fat, as compared to >24 h in control animals. The abundance of apo B-100 protein in CGS 23425-treated hyperlipidemic rats decreased in a dose-dependent manner, but levels of apo B-48 were not significantly affected. Like -triiodothyronine (-T 3 ), treatment with 30 µg/kg CGS 23425 for 6 or 9 days decreased the levels of apo B-100 protein by 80% and 40% respectively. This change was paralleled by a 27% reduction in hepatic apo B-100 mRNA. To investigate a potential mechanism of CGS 23425 action, we measured in vitro apo B mRNA editing activity in hepatocellular extract from control or CGS 23425-treated rats. Treatment with CGS 23425 increased activity of the hepatic apo B-100 editosome, apobec-1. In human hepatoma cells which lack apobec-1 activity, apo B-100 mRNA levels remained the same in cells treated with or without the agent. In summary, these observations 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.

Nuclear Receptors and Their Selective Pharmacologic Modulators

“…9), was shown to lower LDL in hypercholesterolemic rats and Nuclear Receptors and Their Selective Modulators to increase the number of LDL receptors, decrease apolipoprotein B (apoB)-100 levels, and increase apolipoprotein A1 (apoAI) expression (Taylor et al, 1997;Wada et al, 2000).…”

Recent Advances in the Development of Agonists Selective for β1-Type Thyroid Hormone Receptor

“…[hydroxy]methyl]-4-hydroxyphenoxy]-3,5-dimethylphenylamino]-2-oxoacetate (4, Axitirome, CGS-26214) and N-[3,5dimethyl-4-(4-hydroxy-3-isopropylphenoxy)-phenyl]oxamic acid (CGS-23425, 5) was one of the most important members of a new extensively studied class of R 1 -position oxamic acid thyromimetics [29][30][31][32] (Fig. (4)).…”

Induction of the adrenoleukodystrophy-related gene (ABCD2) by thyromimetics

“…Moreover, both GC-1 [30][31][32] and CGS 23425 [41] were demonstrated to mediate hypocholesterolemia in vivo. That should result in a subsequent activation of SREBP (sterol regulatory element-binding protein) (for a review, see [42]).…”