Impact of adipose tissue on plasma plasminogen activator inhibitor-1 in dieting obese women

The increased incidence of cardiovascular diseases in obese subjects could be partially attributed to impaired fibrinolysis due to elevated plasma lev els of tissue plasminogen activator inhibitor 1 (PAI-1), The associations b etween changes in plasma PAI-1, metabolic variables, and adipose tissue dur ing weight loss and regain were studied in 52 healthy, premenopausal, obese women participating in a weight reduction program with a hypocaloric diet. PAI-1, insulin, triglyceride, leptin, and adipsin levels were determined a t entry, after the first week, after completion of the program, and after 5 months of follow-up. In the 33 obese women who completed the program, decr eases in PAI-1 antigen (-54%), PAI activity (-74%), and leptin (-51%), but not of adipsin, were observed. Changes in PAI-1 were associated with change s in body mass index (BMI), body fat, leptin, and insulin. The decreased le vel of PAI-1 remained low after follow-up in the 14 women who maintained th eir reduced weight but increased in the 16 women who regained weight. This increase in PAI-1 was correlated with an increase in body fat and leptin. O n multivariate analysis, BMI was the major determinant of PAI-1 level. In c onclusion, during weight reduction with a hypocaloric diet, the decrease in PAI-1 is more closely related to changes in adipose tissue than to changes in metabolic variables, suggesting a significant role for adipose tissue i n regulating plasma levels of PAI-1.