Licinio J, Mantzoros C, Negrão A B, Cizza G, Wong M L, Bongiorno P B, Chrousos G P, Karp B, Allen C, Flier J S, Gold P W
Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1284, USA.
Nat Med. 1997 May;3(5):575-9. doi: 10.1038/nm0597-575.
Leptin communicates nutritional status to regulatory centers in the brain. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation between rapid fluctuations in plasma levels of leptin and those of adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for on the basis of glucocorticoid suppression of leptin. As leptin levels are pulsatile, we propose that a key function of the CNS is regulated by a peripheral pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414 plasma samples collected every 7 minutes for 24 hours from one obese woman and one normal-weight woman. We found that high leptin levels in the obese subject were due solely to increased leptin pulse height; all concentration-independent pulsatility parameters were almost identical in the two women. Leptin pulsatility therefore can be preserved in the obese.
瘦素将营养状况传递给大脑中的调节中枢。由于外周瘦素会影响高度脉冲式的肾上腺和性腺轴的活性，我们试图确定血液中的瘦素水平是否具有脉冲性。我们对六名健康男性每7分钟测量一次循环瘦素水平，持续24小时，发现总循环瘦素水平呈现出脉冲式释放的模式，每24小时有32.0±1.5次脉冲，脉冲持续时间为32.8±1.6分钟。我们还发现瘦素血浆水平的快速波动与促肾上腺皮质激素（ACTH）和皮质醇的快速波动之间存在负相关，而这种负相关无法用糖皮质激素对瘦素的抑制作用来解释。由于瘦素水平具有脉冲性，我们提出中枢神经系统的一个关键功能受外周脉冲信号调节。在另一项初步研究中，我们比较了从一名肥胖女性和一名正常体重女性身上每7分钟采集一次、持续24小时的414份血浆样本中的瘦素脉冲性。我们发现肥胖受试者的高瘦素水平完全是由于瘦素脉冲高度增加所致；两名女性中所有与浓度无关的脉冲性参数几乎相同。因此，瘦素脉冲性在肥胖者中可以保留。
