Plasma plasminogen activator inhibitor-I is associated with plasma leptin irrespective of body mass index, body fat mass, and plasma insulin and metabolic parameters in premenopausal women

Leptin, the satiety hormone expressed almost exclusively in adipose tissue, is a marker of body fat accumulation in humans. Recent studies have shown that plasminogen activator inhibitor-1 (PAI-1), a prothrombotic factor asso ciated with atherosclerosis complications, is also produced in adipose tiss ue. The objective of the present study was to determine whether PAI-1 antig en plasma concentrations are associated with leptin plasma levels or the bo dy fat mass (FM) independently of the variables known to influence PAI-1 pr oduction. Sixty-one nondiabetic women aged 18 to 45 years with a wide range of values for the body mass index ([BMI] 18.1 to 37.7 kg/m(2)) were evalua ted for (1) body FM and fasting plasma levels of (2) PAI-1 antigen, (3) PAI -1 activity, (4) leptin, (5) insulin, (6) blood glucose, and (7) lipids (ch olesterol, high-density lipoprotein [HDL]-cholesterol, and triglycerides [T G]). Body FM and fat-free mass (FFM) were estimated during fasting conditio ns by the bioimpedance analysis (BIA) method using a tetrapolar device. Bod y fat distribution was evaluated by the waist circumference and the waist t o hip ratio (WHR). FM was directly associated with both PAI-I antigen (r = .585, P < .001) and PAI-1 activity (r = .339, P < .001). Seemingly, leptin was positively related to both PAI-1 antigen (r = .630, P < .001) and PAI-1 activity (r = .497, P < .001). Moreover, both PAI-I antigen and PAI-1 acti vity were directly correlated with FFM (r = .285, P < .05, and r = .336, P < .01, respectively), BMI (r = .594, P < .001, and r = .458, P < .001, resp ectively), and WHR (r = .510, P < .001, and r = .391, P < .005, respectivel y). Insulin was directly related to PAI-T antigen (r = .540, P < .001), PAI -1 activity (r = .259, P < .05), leptin (r = .447, P < .001), and FM (r = . 435, P < .001). The association between PAI-1 antigen (dependent variable) and leptin or FM was tested by a stepwise regression model simultaneously i ncluding leptin, FM, BMI, WHR, age, FFM, and fasting insulin, blood glucose , TG, cholesterol, and HDL-cholesterol as independent variables. PAI-1 anti gen maintained a significant positive independent relationship only with le ptin (t = 2.923, P < .01), insulin (t = 3.489, P < .001), and fasting blood glucose (t = 2.092, P < .05), and a negative independent relationship with HDL-cholesterol (t = -2.634, P < .05). In conclusion, the strong relations hip between PAI-1 antigen and leptin irrespective of other variables known to influence these factors seems to indicate that leptin per se may potenti ally increase PAI-1 plasma concentrations in obese subjects. Copyright (C) 1999 by W.B. Saunders Company.