OBJECTIVE: To examine the effect of diet with exercise on serum leptin and whether leptin is associated with the metabolic syndrome X in a high risk population such as overweight postmenopausal women. STUDY DESIGN AND SUBJECTS: 121 healthy overweight, postmenopausal women (aged 49 to 58y, body mass index (BMI) 25 to 42 kg/m2) were randomized to: a low-energy-diet, 4.2 MJ/d (n = 51), low-energy-diet plus standardized physical exercise (n = 49) or no intervention (control; n = 21) for 12 weeks, followed by 6 months follow-up without intervention. MEASUREMENTS: S-leptin was measured by Radio Immuno Assay (RIA), body composition and fat distribution by dual energy x-ray absorptiometry (DEXA) and anthropometry. Factors associated with the metabolic syndrome X and sex hormones were measured. RESULTS: S-leptin was two-fold higher than in normal-weight postmenopausal women and S-leptin was normalized after weight loss induced by the 12-week low-energy-diet, without any additive effect of the exercise. Of the factors associated with the metabolic syndrome X, serum-leptin correlated significantly only with sex-hormone-binding-globulin and plasminogen-activator-inhibitor-1, whereas factors associated with obesity per se correlated significantly with leptin. Changes in S-leptin correlated with changes in fat tissue mass during the follow-up, but not during the intervention. S-leptin at baseline did not correlate with either short term or long term weight loss. CONCLUSION: There is no effect of exercise added to diet on S-leptin in overweight postmenopausal women. Leptin does not seem to be associated with the metabolic syndrome X, but rather with fatness. S-leptin is probably associated with both dynamic and static effects of adipose tissue. S-leptin did not predict weight loss.

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