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  • Title: Concentration-dependent stimulatory and inhibitory effect of troglitazone on insulin-induced fatty acid synthase expression and protein kinase B activity in 3T3-L1 adipocytes.
    Author: Barthel A, Krüger KD, Roth RA, Joost HG.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 2002 Apr; 365(4):290-5. PubMed ID: 11919653.
    Abstract:
    In order to study the effect of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist troglitazone on the insulin-induced expression of fatty acid synthase (FAS) in adipocytes, we generated a 3T3-L1 cell line stably expressing a FAS reporter gene construct. In this cell line, a low concentration of troglitazone (250 nM) increased the effect of insulin on the FAS promoter activity and the expression of FAS protein about 1.5- to 2-fold. Since the effect of insulin on the expression of FAS is believed to be mediated by activation of protein kinase B (PKB), we investigated the effect of troglitazone on the regulation of PKB. Troglitazone (250 nM) increased the maximal effect of insulin on PKB activity about twofold without significantly affecting its EC(50) (1.4+/-0.5 nM vs. 2.2+/-0.6 nM in controls). Higher concentrations of troglitazone (> or =1 microM) inhibited both insulin-stimulated PKB activity and expression of FAS. In summary, our data indicate a dual effect of troglitazone on the insulin-induced FAS gene expression in 3T3-L1 cells. The therapeutic, stimulatory effect is produced by low concentrations of troglitazone (250 nM), and is presumably mediated by enhanced activation of PKB.
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