Troglitazone reduces plasminogen activator inhibitor-1 expression and secretion in cultured human adipocytes.
OBJECTIVE
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-gamma, 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 microgram/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).


CONCLUSIONS
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.
Gottschling-Zeller
H
H
Diabetes Research Institute, Heinrich-Heine-University Düsseldorf, Germany.
Röhrig
K
K
Hauner
H
H
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003470:Culture Media / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D009852:Omentum; D009994:Osmolar Concentration; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D012867:Skin; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D003470:Culture Media; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone