Transcription factor STAT3 in leptin target neurons of the rat hypothalamus

Transcription factor STAT3 in leptin target neurons of the rat hypothalamus
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DOI:
10.1159/000054392
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发表时间:
1998-12-01
期刊:
影响因子:
4.1
通讯作者:
Meister, B
Meister, B
中科院分区:
医学2区
文献类型:
--
作者:
Häkansson, ML;Meister, B

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瘦素是一种脂肪组织源性激素,通过与表达特定瘦素受体(Ob-R)的下丘脑神经回路相互作用来调节体重。Ob-Rs通过JAK-STAT(Janus激酶信号转导和转录激活子)信号转导途径发挥作用。最近的证据表明,转录因子STAT3主要介导瘦素在下丘脑的作用。我们用兔多克隆STAT3抗血清,用间接免疫荧光组织化学方法研究了STAT3蛋白在大鼠下丘脑的存在和细胞定位。该抗血清通过Western blotting在大鼠下丘脑匀浆上鉴定出一个92 kDa的蛋白,与STAT3的预期大小相对应。STAT3免疫反应阳性神经元见于室旁核(小细胞部)、室周核、弓状核和下丘脑外侧区的Ob-R神经元。直接双标结果显示,在弓状核腹内侧部的神经肽Y(NPY)阳性神经元和弓状核腹外侧部(POMC)的前阿片黑素皮质素(POMC)阳性神经元中均有STAT3免疫反应阳性。这些结果为STAT3在弓状核含Ob-R的NPY和POMC神经元以及室旁核和下丘脑外侧区含Ob-R的神经元中的瘦素作用提供了解剖学基础。
Leptin is an adipose tissue-derived hormone that regulates body weight via interactions with hypothalamic neuronal circuitries expressing specific leptin receptors (Ob-R). The Ob-Rs act via the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway of signal transduction. Recent evidence suggests that primarily the transcription factor STAT3 mediates leptin's action in the hypothalamus. We have investigated the presence and cellular localization of STAT3 protein in the rat hypothalamus by means of indirect immunofluorescence histochemistry using a rabbit polyclonal STAT3 antiserum. The antiserum identified a 92-kDa protein using Western blotting on rat hypothalamic homogenates, corresponding to the expected size of STAT3. STAT3 immunoreactivity was demonstrated in Ob-R-containing neurons of the paraventricular nucleus (parvocellular part), periventricular nucleus, arcuate nucleus and in the lateral hypothalamic area. Direct double-labeling showed presence of STAT3 immunoreactivity in neuropeptide Y (NPY)-containing neurons of the ventromedial part of the arcuate nucleus and in proopiomelanocortin (POMC)-containing neurons of the ventrolateral part of the arcuate nucleus. The results provide an anatomical basis for a leptin action mediated by STAT3 in Ob-R-containing NPY and POMC neurons of the arcuate nucleus, as well as by Ob-R-containing neurons of the parvocellular paraventricular nucleus and lateral hypothalamic area.