Leptin does not play a major role in platelet aggregation in obesity and leptin deficiency

Objective: A recent study suggested that high concentrations of leptin enhance platelet aggregations. Therefore, the aim of this study was to investigate whether platelet aggregation is altered in patients with leptin gene mutations compared with obese subjects or controls. Research Methods and Procedures: Four men (one homozygous man and his three heterozygous brothers) carrying a leptin gene mutation; 20 age-matched, healthy, unrelated men; and 18 age-matched obese men were enrolled in the study. Adenosine diphosphate (ADP)-, collagen-, and epinephrine-induced platelet aggregation were evaluated in all individuals. Results: Our results show that patients with the leptin gene mutation (both the homozygous and heterozygous patients) had significantly higher ADP-induced (78.3 +/- 3.4% vs. 57.9 +/- 9.3%, p = 0.001), collagen-induced (78.1 +/- 2.9% vs. 56.7 +/- 9.3%, p = 0.007), and epinephrine-induced (76.5 +/- 9.2% vs. 59.5 +/- 7.70%, p = 0.003) platelet aggregation compared with controls. However, ADP-, collagen-, or epinephrine-induced platelet aggregations were similar to those in obese patients. Platelet aggregation responses to a combination of pretreatment with leptin at concentrations of 20, 50, 100, or 500 ng/mL for 5 minutes and ADP at concentrations of 2 mu mol/liter also were evaluated. However, we did not find significant increases in platelet aggregation even at high concentrations of leptin (100 or 500 ng/mL) in leptin-deficient patients, obese subjects, or controls. Discussion: Our data show that similar to findings in obese humans, homozygous. or heterozygous. leptin deficiency is associated with increased platelet aggregation compared with controls, and that higher concentrations of leptin do not increase platelet aggregation.