The leptin receptor system of human platelets.
Obesity is associated with elevated levels of leptin in the blood. Elevated leptin is a risk factor for thrombosis in humans, and leptin administration promotes platelet activation and thrombosis in the mouse. The current study examines the effect of leptin on human platelets, and provides initial insights into the nature of the leptin receptor on these platelets. Leptin potentiated the aggregation of human platelets induced by low concentrations of ADP, collagen and epinephrine. However, the response varied significantly between donors, with platelets from some donors (approximately 40%) consistently responding to leptin (responders) and those from other donors (approximately 60%) never responding (non-responders). Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) experiments showed that platelets from both groups only express the signaling form of the leptin receptor, and that responder platelets express higher levels of this receptor than non-responders. Ligand-binding assays demonstrate specific, saturable binding of leptin to platelets from both groups with apparent K(d) values of 76 +/- 20 nM for responders and 158 +/- 46 nM for non-responders. Thus, the decreased sensitivity of non-responder platelets to leptin does not result from the absence of the signaling form of this receptor, but may reflect differences in its level of expression and/or affinity for leptin. These preliminary studies demonstrate that platelets are a major source of leptin receptor in the circulation, and suggest that leptin-responsive individuals may have a higher risk for obesity-associated thrombosis than non-responsive individuals.
Giandomenico
G
G
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Dellas
C
C
Czekay
R-P
RP
Koschnick
S
S
Loskutoff
D J
DJ
D000244:Adenosine Diphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D015992:Body Mass Index; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008024:Ligands; D008297:Male; D046529:Microscopy, Electron, Transmission; D009765:Obesity; D015539:Platelet Activation; D010974:Platelet Aggregation; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013927:Thrombosis; D013997:Time Factors
C515448:LEPR protein, human; D020738:Leptin; D008024:Ligands; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse; D000244:Adenosine Diphosphate; D003094:Collagen; D004837:Epinephrine