Abstract
Aims/hypothesis. Increased plasma plasminogen activator inhibitor-1 (PAI-1) concentrations are characteristic for subjects with insulin resistance and could contribute to the increased cardiovascular risk in this state. In this study, we investigated the effect of troglitazone, a ligand of the nuclear receptor peroxisome proliferator activated receptor-γ, on PAI-1 expression and secretion in human adipocytes.¶Methods. We used two models: in vitro differentiated subcutaneous and omental adipocytes cultured under serum-free conditions and isolated subcutaneous and omental fat cells kept in suspension culture. Plasminogen activator inhibitor-1 protein was measured by ELISA, PAI-1 mRNA by a semiquantitative RT-PCR technique.¶Results. Exposure of in vitro differentiated subcutaneous adipocytes from young normal-weight females to 1 μg/ml troglitazone for 72 h caused a reduction of both PAI-1 secretion (by 29 ± 5 %; p < 0.01) and PAI-1 mRNA expression (by 26 ± 3 %; p < 0.05). In cultures from severely obese subjects, troglitazone induced a decrease of PAI-1 antigen secretion from newly differentiated omental adipocytes by 49 ± 8 % (p < 0.01) and from subcutaneous adipocytes by 30 ± 7 % (p < 0.05). Exposure of freshly isolated subcutaneous and omental adipocytes in suspension culture to troglitazone induced a similar reduction of PAI-1 concentration in the culture medium (by 35 ± 11 %, p < 0.05. and 33 ± 8 %, p < 0.05 compared with control, respectively).¶Conclusion/interpretation. This study provides evidence that troglitazone reduces PAI-1 production in human adipocytes, probably at the transcriptional level. This observation could point to a new beneficial effect of troglitazone, particularly in obese subjects, which could be associated with a reduced cardiovascular risk. [Diabetologia (2000) 43: 377–383]
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Received: 28 September 1999 and in revised form: 11 November 1999
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Gottschling-Zeller, H., Röhrig, K. & Hauner, H. Troglitazone reduces plasminogen activator inhibitor-1 expression and secretion in cultured human adipocytes. Diabetologia 43, 377–383 (2000). https://doi.org/10.1007/s001250050057
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DOI: https://doi.org/10.1007/s001250050057