The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men
The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men
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DOI：
10.1172/jci200317490
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发表时间：
2003-05-01
影响因子：
15.9
通讯作者：
Mantzoros, CS
中科院分区：
文献类型：
--
作者：
Chan, JL;Heist, K;Mantzoros, CS
为了阐明瘦素在急性禁食期间调节神经内分泌和代谢功能中的作用，在四种不同的条件下研究了六到八名健康的瘦男性：一项基线进食状态和三项72小时禁食研究，分别给予安慰剂、低剂量重组甲硫氨酰人瘦素（r-metHuLeptin），或设计成将血清瘦素维持在与进食状态下的水平相似的水平的补充剂量r-metHuLeptin。在禁食期间给予的替代剂量r-metHuLeptin防止饥饿诱导的下丘脑-垂体-性腺轴变化，部分防止下丘脑-垂体-甲状腺轴和血清中IGF-1结合能力的变化。因此，在正常男性中，空腹瘦素的下降可能是这些轴的生理适应所必需的，也是足够的，这些轴需要瘦素水平高于一定的激活阈值。与小鼠的研究结果相反，禁食诱导的下丘脑-垂体-肾上腺、肾素-醛固酮和生长激素-IGF-1轴的变化以及燃料利用可能与人类的瘦素无关。瘦素在正常化几个饥饿引起的神经内分泌变化的作用，可能有重要的意义的病理生理学和饮食失调和肥胖的治疗。
To elucidate the role of leptin in regulating neuroendocrine and metabolic function during an acute fast, six to eight healthy, lean men were studied under four separate conditions: a baseline fed state and three 72-hour fasting studies with administration of either placebo, low-dose recombinant-methionyl human leptin (r-metHuLeptin), or replacement-dose r-metHuLeptin designed to maintain serum leptin at levels similar to those in the fed state. Replacement-dose r-metHuLeptin administered during fasting prevents the starvation-induced changes in the hypothalamic-pituitary-gonadal axis and, in part, the hypothalamic-pituitary-thyroid axis and IGF-1 binding capacity in serum. Thus, in normal men, the fall in leptin with fasting may be both necessary and sufficient for the physiologic adaptations of these axes, which require leptin levels above a certain threshold for activation. In contrast to findings in mice, fasting-induced changes in the hypothalamic-pituitary-adrenal, renin-aldosterone, and growth hormone-IGF-1 axes as well as fuel utilization may be independent of leptin in humans. The role of leptin in normalizing several starvation-induced neuroendocrine changes may have important implications for the pathophysiology and treatment of eating disorders and obesity.