Identifying pathways involved in leptin-dependent aggregation of human platelets

A. Corsonello, A. Malara, D. De Domenico, F. Perticone, A. Valenti, M. Buemi, R. Ientile, F. Corica

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To investigate the role of phospholipase C (PLC), phospholipase A2 (PLA2), calcium, and protein kinase C (PKC) in mediating leptin-enhanced aggregation of human platelets. DESIGN: In vitro, ex vivo study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital of Messina, Italy. SUBJECTS: In total, 14 healthy normal-weight male (age 31.4 ± 1.9 y; body mass index 22.7 ± 0.6kg/m2) subjects. MEASUREMENTS: Adenosine diphosphate-(ADP-) induced platelet aggregation and platelet free calcium were measured after incubation of platelets with leptin alone (5-500 ng/ml), or leptin (50 and 100 ng/ml) in combination with anti-human leptin receptor long form antibody (anti-ObRb-Ab, 1:800-1:100 dilutions), PLC inhibitor U73122 (3.125-25 μM), PLA2 inhibitor AACOCF3 (1.25-10 μM), or PKC inhibitor Ro31-8220 (1.25-10 μM). RESULTS: Platelet stimulation with leptin leads to a significant and dose-dependent increase in ADP-induced platelet aggregation and platelet free calcium concentrations. Leptin effects on both platelet aggregation and calcium mobilization were completely abated by the co-incubation with leptin and anti-ObRb-Ab. Leptin-induced platelet aggregation was dose-dependently inhibited by U73122, AACOCF3, or Ro31-8220. The effect of leptin on intracellular calcium was inhibited in a dose-dependent manner by incubation with U73122 and AACOCF3, but not with Ro31-8220. CONCLUSIONS: Our study confirms that leptin is able to enhance ADP-induced aggregation of human platelets, and raise the possibility that PLC, PKC, PLA2, and calcium could play a relevant role in mediating the proaggregating action of leptin.

Original languageEnglish
Pages (from-to)979-984
Number of pages6
JournalInternational Journal of Obesity
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 2004

Keywords

  • Calcium
  • Leptin
  • Phospholipase A
  • Phospholipase C
  • Platelet aggregation
  • Protein kinase C

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

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