Leptin receptor expressing neurons express phosphodiesterase-3B (PDE3B) and leptin induces STAT3 activation in PDE3B neurons in the mouse hypothalamus.
Leptin receptor expressing neurons express phosphodiesterase-3B (PDE3B) and leptin induces STAT3 activation in PDE3B neurons in the mouse hypothalamus.
复制标题
DOI：
10.1016/j.peptides.2015.08.011
复制
发表时间：
2015-11
期刊：
影响因子：
3
通讯作者：
Sahu A
中科院分区：
文献类型：
--
作者：
Sahu M;Sahu A
下丘脑中的瘦素信号对于正常的食物摄入和体重调节至关重要。越来越多的证据表明，除了信号换能器和转录-3激活器（STAT3）途径外，包括磷酸二酯酶- 3b （PDE3B）途径在内的几种非STAT3途径介导下丘脑的瘦素信号传导。我们已经证明PDE3B定位于与能量稳态调节有关的下丘脑的各个部位，并且瘦素的厌食和体重减轻作用是由PDE3B的激活介导的。PDE3B是否在下丘脑瘦素受体（ObRb）表达神经元的长链中表达，以及瘦素是否在PDE3B表达神经元中诱导STAT3激活，目前尚不清楚。在这项研究中，我们在接受瘦素（5mg/kg, ip）治疗2小时的ObRb- gfp小鼠中，检测了PDE3B与ObRb神经元在不同下丘脑核中的共定位。结果显示，弓形核（ARC, 93%）、腹内侧核（VMN, 94%）、背内侧核（DMN, 95%）、腹侧乳头前核（PMv, 97%）和外侧下丘脑（LH, 97%）的大部分ObRb神经元共表达PDE3B。接下来，我们在接受瘦素（5mg/kg, ip）治疗1小时的C57BL6小鼠下丘脑中检测了p-STAT3和PDE3B的共定位。结果显示，下丘脑不同核区包括ARC、VMN、DMN、LH和PMv区几乎所有p-STAT3阳性神经元均表达PDE3B。这些结果提示PDE3B通路在调节下丘脑瘦素作用中可能起直接作用。
Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. Cumulative evidence suggests that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways including the phosphodiesterase-3B (PDE3B) pathway mediate leptin signaling in the hypothalamus. We have shown that PDE3B is localized in various hypothalamic sites implicated in the regulation of energy homeostasis and that the anorectic and body weight reducing effects of leptin are mediated by the activation of PDE3B. It is still unknown if PDE3B is expressed in the long form of the leptin-receptor (ObRb)-expressing neurons in the hypothalamus and whether leptin induces STAT3 activation in PDE3B-expressing neurons. In this study, we examined co-localization of PDE3B with ObRb neurons in various hypothalamic nuclei in ObRb-GFP mice that were treated with leptin (5mg/kg, ip) for 2 hr. Results showed that most of the ObRb neurons in the arcuate nucleus (ARC, 93%), ventromedial nucleus (VMN, 94%), dorsomedial nucleus (DMN, 95%), ventral premammillary nucleus (PMv, 97%) and lateral hypothalamus (LH, 97%) co-expressed PDE3B. We next examined co-localization of p-STAT3 and PDE3B in the hypothalamus in C57BL6 mice that were treated with leptin (5mg/kg, ip) for 1 hr. The results showed that almost all p-STAT3 positive neurons in different hypothalamic nuclei including ARC, VMN, DMN, LH and PMv areas expressed PDE3B. These results suggest the possibility for a direct role for the PDE3B pathway in mediating leptin action in the hypothalamus.