Differential accessibility of circulating leptin to individual hypothalamic sites

Differential accessibility of circulating leptin to individual hypothalamic sites
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DOI：
10.1210/en.2007-0655
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发表时间：
2007-11-01
期刊：
ENDOCRINOLOGY
影响因子：
4.8
通讯作者：
Muenzberg, Heike
Muenzberg, Heike
中科院分区：
医学2区
文献类型：
--
作者：
Faouzi, Miro;Leshan, Rebecca;Muenzberg, Heike

文献摘要

被引文献

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表达长型瘦素受体（LRb）的下丘脑神经元介导重要的瘦素作用。虽然它已被建议，瘦素穿过血脑屏障（BBB）通过一个特定的运输系统，我们假设存在一个人口的下丘脑弓状核（ARC）的神经元，感觉瘦素独立于这个运输系统。事实上，内源性循环瘦素导致ARC/LRb神经元群体中可检测水平的基线激活的信号转导子和转录激活子3（STAT 3）磷酸化，这与这些神经元中与其他LRb神经元相比循环瘦素的感知增加一致。此外，ARC/LRb神经元的人口，响应更迅速，更敏感的循环瘦素相比，其他下丘脑LRb神经元检测瘦素激活磷酸化STAT 3。此外，外周应用BBB不渗透性逆行示踪剂荧光金显示了直接接触循环的ARC/LRb神经元群（例如，G.通过到达BBB外的神经元过程）。两者合计，这些数据表明，ARC/LRb神经元的人口直接接触的循环，并显示增加的敏感性循环瘦素相比，神经元完全居住在下丘脑其他地方的BBB后面。
Hypothalamic neurons expressing the long form of the leptin receptor (LRb) mediate important leptin actions. Although it has been suggested that leptin crosses the blood-brain barrier (BBB) via a specific transport system, we hypothesized the existence of a population of hypothalamic arcuate nucleus (ARC) neurons that senses leptin independently of this transport system. Indeed, endogenous circulating leptin results in detectable levels of baseline activated signal transducer and activator of transcription 3 (STAT3) phosphorylation in a population of ARC/LRb neurons, consistent with increased sensing of circulating leptin in these neurons compared with other LRb neurons. Furthermore, a population of ARC/LRb neurons that responds more rapidly and sensitively to circulating leptin compared with other hypothalamic LRb neurons detected by leptin activated phosphorylated STAT3. In addition, peripheral application of the BBB-impermeant retrograde tracer fluorogold revealed a population of ARC/LRb neurons that directly contact the circulation (e. g. via neuronal processes reaching outside the BBB). Taken together, these data suggest that a population of ARC/LRb neurons directly contacts the circulation and displays increased sensitivity to circulating leptin compared with neurons residing entirely behind the BBB elsewhere in the hypothalamus.