Leptin promotes aggregation of human platelets via the long form of its receptor.
Plasma leptin levels are elevated in most obese individuals, and obesity is accompanied by a high incidence of cardiovascular disease. Therefore, leptin could be involved in the pathogenesis of cardiovascular disease. In the present study, the role of leptin was explored in the regulation of platelet function. The expression of the long form of the leptin receptor was detected in human platelets. At 50 ng/ml, human leptin induced phosphorylation of several proteins of platelets at the tyrosine residue. Neither leptin at concentrations < or = 100 ng/ml nor ADP at concentrations > or = 1 micromol/l affected platelet aggregation. However, after pretreatment with 100 ng/ml leptin for 5 min, 1 micromol/l ADP caused aggregation. Thus, leptin and ADP acted synergistically. At a concentration of 2 micromol/l, ADP induced platelet aggregation, which was markedly enhanced by 30-100 ng/ml leptin in a concentration-dependent manner. This concentration range corresponds to that of plasma leptin levels in obese individuals. At the lower concentrations (< 10 ng/ml) that are observed in normal individuals, leptin had no effect on platelet aggregation. In conclusion, leptin at high concentrations has the novel function of promoting platelet aggregation, which may be a key coupling factor between obesity and the cardiovascular disease associated with syndrome X and diabetes.
Nakata
M
M
Department of Laboratory Medicine, Kagoshima University School of Medicine, Japan.
Yada
T
T
Soejima
N
N
Maruyama
I
I
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D004357:Drug Synergism; D006801:Humans; D020738:Leptin; D009994:Osmolar Concentration; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D011506:Proteins / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
D001798:Blood Proteins; D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000244:Adenosine Diphosphate