Abstract.
In order to study the effect of the peroxisome proliferator-activated receptor gamma (PPARγ) 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 EC50 (1.4±0.5 nM vs. 2.2±0.6 nM in controls). Higher concentrations of troglitazone (≥1 µM) 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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Barthel, A., Krüger, KD., Roth, R.A. et al. Concentration-dependent stimulatory and inhibitory effect of troglitazone on insulin-induced fatty acid synthase expression and protein kinase B activity in 3T3-L1 adipocytes. Naunyn-Schmiedeberg's Arch Pharmacol 365, 290–295 (2002). https://doi.org/10.1007/s00210-002-0529-y
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DOI: https://doi.org/10.1007/s00210-002-0529-y