Apolipoprotein A-I expression in rats is not altered by troglitazone.
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 (G(3)PDH) 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 alpha activity in addition to their PPAR gamma effects, may well be able to induce apoA-I expression.
Mooradian
Arshag D
AD
The Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, St. Louis University Medical School, St. Louis, MO 63104, USA. mooradad@slu.edu
Haas
Michael J
MJ
Chehade
Joe
J
Wong
Norman C W
NC
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D001835:Body Weight; D002839:Chromans / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D016632:Apolipoprotein A-I; D002839:Chromans; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone