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 enha nce platelet aggregations. Therefore, the aim of this study was to investig ate whether platelet aggregation is altered in patients with leptin gene mu tations 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, he althy, unrelated men; and 18 age-matched obese men were enrolled in the stu dy. Adenosine diphosphate (ADP)-, collagen-, and epinephrine-induced platel et 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-ind uced (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 contro ls. 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 als o were evaluated. However, we did not find significant increases in platele t aggregation even at high concentrations of leptin (100 or 500 ng/mL) in l eptin-deficient patients, obese subjects, or controls. Discussion: Our data show that similar to findings in obese humans, homozyg ous. or heterozygous. leptin deficiency is associated with increased platel et aggregation compared with controls, and that higher concentrations of le ptin do not increase platelet aggregation.