Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation

Abstract

Context: Leptin is a nutritionally regulated adipocyte-derived cytokine. Previous studies in obese patients have demonstrated increased inflammatory markers and increased platelet aggregation in association with leptin. However, the effects of leptin administration on markers of inflammation and platelet aggregation in a human model of undernutrition have not previously been studied. Objective: The objective of the study was to investigate markers of inflammation, platelet activation, and platelet aggregation in a model of caloric deprivation and increased leptin sensitivity. Design: This study was a randomized, placebo-controlled study conducted between November 2002 and November 2003. Setting: The study was conducted at an inpatient care setting at the General Clinical Research Center. Participants: Twenty healthy, young (18-35 yr old), normal-weight (body mass index, 20-26 kg/m2) women were recruited from local advertisements. No subjects withdrew due to adverse effects. Intervention: The effects of physiological recombinant methionyl human leptin or identical placebo administration were investigated over a 4-d fast. Main Outcome Measures: The primary outcome measures for this study were C-reactive protein (CRP) and indices of platelet activity. Results: Leptin administration prevented the fasting-induced decline in leptin (P < 0.05 vs. placebo at each time point). Leptin administration increased CRP (6.3 ± 2.4 vs. 0.7 ± 0.3 mg/liter; P = 0.04), circulating P-selectin (11.6 ± 10.2 vs. -28.9 ± 15.6 ng/ml; P = 0.04), and induction of platelet aggregation (5.8 ± 2.6 vs. -2.7 ± 2.9%, P = 0.04, percent maximum platelet aggregation) relative to placebo administration (change in leptin vs. change in placebo, respectively, for each variable). Leptin tended to increase serum amyloid A [0.1 ± 0.2 vs. -0.3 ± 0.1 log 10 (ng/ml); P = 0.07], and the changes in serum amyloid A and CRP were highly correlated (r = 0.83; P < 0.0001). No changes in TNFα, IL-6, IL-10, plasminogen activator inhibitor-1, haptoglobin, intercellular adhesion molecule, or vascular cell adhesion molecule were seen between the groups. Conclusions: Our data provide evidence that physiological leptin administration stimulates inflammatory and platelet responses in humans during caloric deprivation. Copyright © 2005 by The Endocrine Society.