Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans
Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans
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DOI：
10.1073/pnas.0505429103
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发表时间：
2006-05-30
影响因子：
11.1
通讯作者：
Mantzoros, Christos S.
中科院分区：
文献类型：
--
作者：
Chan, Jean L.;Matarese, Giuseppe;Mantzoros, Christos S.
为了阐明瘦素在健康人短期饥饿期间调节神经内分泌和免疫功能的作用是否是允许的，即仅当循环瘦素水平低于临界阈值水平时才发生，我们研究了七名正常体重的女性，她们处于正常瘦素饮食状态和由 72 小时禁食诱导的两种相对低瘦素血症状态，在此期间我们给予安慰剂或重组体 替代剂量的甲硫氨酰人瘦素（r-metHuLeptin）。禁食 72 小时使瘦素水平降低约 80%，从生理中期 (14.7 +/- 2.6 ng/ml) 降至生理低 (2.8 +/- 0.3 ng/ml) 水平。禁食期间服用 r-metHuLeptin 可将瘦素完全恢复至生理水平 (28.8 +/- 2.0 ng/ml)，并逆转禁食相关的夜间黄体生成激素脉冲频率的下降，但对禁食引起的促甲状腺激素脉冲、甲状腺和 IGF-1 激素水平、下丘脑-垂体-肾上腺的变化没有影响 和肾素醛固酮活性。 FSH 和性类固醇水平没有改变。瘦素水平的短期降低会减少适应性免疫反应的循环细胞数量，但 r-metHuLeptin 对其数量或体外功能没有重大影响。因此，瘦素水平在生理范围内的变化对于瘦素充足的人类没有重大的生理影响。需要涉及更严重和/或慢性瘦素缺乏的研究来精确定义每个瘦素生理目标的正常瘦素水平的下限。
To elucidate whether the role of leptin in regulating neuroendocrine and immune function during short-term starvation in healthy humans is permissive, i.e., occurs only when circulating leptin levels are below a critical threshold level, we studied seven normal-weight women during a normoleptinemic-fed state and two states of relative hypoleptinemia induced by 72-h fasting during which we administered either placebo or recombinant methionyl human leptin (r-metHuLeptin) in replacement doses. Fasting for 72 h decreased leptin levels by approximate to 80% from a midphysiologic (14.7 +/- 2.6 ng/ml) to a low-physiologic (2.8 +/- 0.3 ng/ml) level. Administration of r-metHuLeptin during fasting fully restored leptin to physiologic levels (28.8 +/- 2.0 ng/ml) and reversed the fasting-associated decrease in overnight luteinizing hormone pulse frequency but had no effect on fasting-induced changes in thyroid-stimulating hormone pulsatility, thyroid and IGF-1 hormone levels, hypothalamic-pituitary-adrenal and renin-aldosterone activity. FSH and sex steroid levels were not altered. Shortterm reduction of leptin levels decreased the number of circulating cells of the adaptive immune response, but r-metHuLeptin did not have major effects on their number or in vitro function. Thus, changes of leptin levels within the physiologic range have no major physiologic effects in leptin-replete humans. Studies involving more severe and/or chronic leptin deficiency are needed to precisely define the lower limit of normal leptin levels for each of leptin's physiologic targets.