Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation
Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation
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DOI：
10.1210/jc.2005-0780
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发表时间：
2005-10-01
影响因子：
5.8
通讯作者：
Grinspoon, S
中科院分区：
文献类型：
--
作者：
Canavan, B;Salem, RO;Grinspoon, S
背景：瘦素是一种营养调节的脂肪细胞衍生细胞因子。先前对肥胖患者的研究表明，炎症标志物增加和血小板聚集增加与瘦素相关。然而，此前尚未研究过瘦素给药对人类营养不良模型中炎症和血小板聚集标志物的影响。 目的：本研究的目的是在热量剥夺和瘦素敏感性增加的模型中研究炎症、血小板活化和血小板聚集标志物。设计：本研究是一项于 2002 年 11 月至 2003 年 11 月期间进行的随机、安慰剂对照研究。 背景：该研究在综合临床研究中心的住院护理环境中进行。 参与者：从当地广告中招募了 20 名健康、年轻（18-35 岁）、体重正常（体重指数为 20-26 kg/m(2)）的女性。没有受试者因不良反应而退出。干预：在 4 天禁食期间研究生理重组甲硫氨酰人瘦素或相同安慰剂给药的影响。主要结果指标：本研究的主要结果指标是 C 反应蛋白 (CRP) 和血小板活性指数。结果：瘦素给药可防止禁食引起的瘦素下降（每次与安慰剂相比，P < 0.05） 观点）。瘦素给药增加了CRP（6.3 +/- 2.4 vs. 0.7 +/- 0.3 mg/l；P = 0.04）、循环P-选择素（11.6 +/- 10.2 vs. -28.9 +/- 15.6 ng/ml；P = 0.04），并诱导血小板聚集（5.8 +/- 2.6 vs. -2.7 +/- 2.9%， P = 0.04，最大平板百分比 elet 聚合）相对于安慰剂给药（每个变量分别是瘦素的变化与安慰剂的变化）。瘦素倾向于增加血清淀粉样蛋白 A [0.1 +/- 10.2 vs. -0.3 +/- 0.1 log(10) (ng/ml)； P = 0.07]，且血清淀粉样蛋白A与CRP的变化高度相关（r = 0.83；P < 0.0001）。各组之间未观察到 TNF α、IL-6、IL-10、纤溶酶原激活剂抑制剂 1、触珠蛋白、细胞间粘附分子或血管细胞粘附分子的变化。 结论：我们的数据提供了证据，证明生理性瘦素给药在热量剥夺期间会刺激人体的炎症和血小板反应。
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/m(2)) 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 plat elet 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 +/- 10.2 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 TNF alpha, 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.