Recent studies have suggested that
leptin, a
plasma protein secreted by adipocytes, may play a role in artherothrombosis. In this study, we tested the hypothesis that
leptin contributes to in vivo endothelial dysfunction in obese subjects. A cross-sectional comparison of plasma
leptin, soluble
thrombomodulin (sTM) and soluble vascular adhesion molecule-1 (VCAM-1) was carried out in 35 obese women (age 48+/-13) selected with a body mass index (BMI) > or =30kg/m(2) and 25 normal weight women (age 50+/-11, BMI < 25). An additional study was conducted to determine the short-term effects of
weight loss induced by
caloric restriction. Plasma levels of
leptin, sTM and sVCAM-1 were measured before and after
weight loss. Obese women had higher levels of
leptin (35+/-22 versus 22+/-19, P<0.01), sTM (4.8+/-1.8 versus 1.9+/-1.5, P<0.001) and sVCAM-1 (726+/-109 versus 583+/-50, P<0.001) than non-obese women. sTM and sVCAM-1 concentrations had a positive correlation with BMI (sTM, r=0.70, P<0.001; sVCAM-1, r=0.60, P<0.001), waist circumference (sTM, r=0.66, P<0.001; sVCAM-1, r=0.37, P<0.01) and
leptin levels (sTM, r=0.53, P<0.001; sVCAM-1, r=0.42, P<0.005). At multiple regression analysis
leptin predicted sTM and sVCAM-1 independently of
obesity measures and other covariates. Twenty-nine obese patients who completed the program of
weight reduction showed a significant decrease in
leptin, sTM, and sVCAM-1 levels. The magnitude of decrease of sTM and sVCAM-1 was related to the magnitude of reduction in
leptin levels. Therefore, our results show that
obesity is associated with enhanced levels of
atherosclerosis markers. These abnormalities are related to
abdominal obesity possibly mediated by
leptin levels, and are reversible with
weight loss.