Leptin-dependent platelet aggregation in healthy, overweight and obese subjects.
OBJECTIVE
To investigate the effects of leptin on platelet aggregation and platelet free calcium (Ca(2+)) concentrations, and the role of the long form of leptin receptor (ObRb) and the phospholipase C (PLC) in mediating leptin effects on platelet function.


METHODS
Cross-sectional, clinical study.


METHODS
Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital of Messina, Italy.


METHODS
A total of 19 healthy, 14 overweight, and 16 obese male subjects.


METHODS
ADP-induced platelet aggregation and platelet Ca(2+) were measured after incubation of platelet-rich plasma with leptin alone 5-200 ng/ml, leptin 200 ng/ml and anti-human leptin receptor long-form antibody (ObRb-Ab) 5-10 microl, or leptin 200 ng/ml and PLC inhibitor U73122 0.5-1 nmol/l.


RESULTS
Platelet stimulation with leptin lead to a significant and dose-dependent increase in platelet aggregation in healthy subjects. This effect was blunted in overweight, and strongly reduced in obese subjects. Similarly, the incubation with leptin induced a significant and dose-dependent increase in platelet free calcium, which was blunted in overweight and obese patients. The effect of leptin on platelet aggregation and platelet Ca(2+) was completely abated by the anti-ObRb-Ab and the PLC inhibitor U73122.


CONCLUSIONS
Leptin produces a dose-dependent enhancement of ADP-induced platelet aggregation in humans. Platelet aggregation response to leptin is blunted, but not completely abolished in overweight/obese subjects, thus suggesting that platelet may represent a site of leptin resistance in human obesity. Leptin increases platelet free calcium in a dose-dependent manner. The inhibition of PLC completely abates the effect of leptin on both platelet aggregation and Ca(2+) levels. These findings suggest that signaling pathway other than JAK-STAT tyrosine phosphorylation (ie PLC and calcium) may be involved in mediating the prothrombotic action of leptin.
Corsonello
A
A
Italian National Research on Aging (INRCA), Cosenza, Italy. andrea_corsonella@tin.it
Perticone
F
F
Malara
A
A
De Domenico
D
D
Loddo
S
S
Buemi
M
M
Ientile
R
R
Corica
F
F
D000244:Adenosine Diphosphate / Q000097:blood; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D002118:Calcium / Q000097:blood; D003430:Cross-Sectional Studies; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000502:physiology; D054411:Receptors, Leptin; D010738:Type C Phospholipases / Q000502:physiology
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000244:Adenosine Diphosphate; D010738:Type C Phospholipases; D002118:Calcium