Apolipoprotein A-I Expression in Rats is Not Altered by Troglitazone 1

Abstract

Insulin is known to upregulate apolipoprotein A-I (apoA-I) promoter activity and to increase apoA1 gene expression in vivo. To determine if enhancement of insulin action with insulin sensitizers can also increase the apoA-I expression, we studied the in vivo effect of troglitazone, a potent insulin sensitizer, on the expression of rat hepatic and intestinal apoA-I mRNA using Northern blot analysis. The plasma, hepatic, and intestinal apoA-I content was also measured with immunoblot analysis using a specific anti-rat apoA-I antiserum. Troglitazone, given mixed with rat chow (0.2%) for 18 days, did not Increase either plasma or tissue apoA-I mRNA or protein content. Intestinal apoA-I mRNA content relative to glyceraldehyde-3 phosphate dehydrogenase (G₃PDH) mRNA was significantly lower compared with hepatic tissue content in both control and troglitazone-treated rats. The effect of troglitazone on the rat apoA-I promoter was examined using transient transfection analysis in HepG2 cells transfected with the apoA-I-chloramphenicol acetyl transferase (CAT) reporter plasmid (pAI.474.CAT). CAT activity (percentage acetylation of chloramphenicol as means ± SEM) was not significantly different in ethanol (vehicle)-treated cells compared with cells treated with troglitazone (50.5% ± 2.5% in control cells vs 57.7% ± 8.2% and 53.5% ± 4.2% in cells treated with 10 and 100 mM troglitazone, respectively). It is concluded that troglitazone doses Known to achieve insulin sensitization did not enhance rat apoA-I promoter activity sufficiently to result in an increased apoA-I mRNA or protein expression in the Intact rat. However, peroxisome proliferator activator receptor (PPAR) agonists that have significant PPAR α activity in addition to their PPAR γ effects, may well be able to induce apoA-I expression.