Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action
Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action
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DOI：
10.1152/ajpendo.00643.2012
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发表时间：
2013-05-01
影响因子：
5.1
通讯作者：
Muenzberg, Heike
中科院分区：
文献类型：
--
作者：
Laque, Amanda;Zhang, Yan;Muenzberg, Heike
瘦素通过表达瘦素受体(LepRb)的神经元起中枢作用，调节食物摄入、能量消耗和其他生理功能。LepRb神经元在大脑中随处可见，几个不同的群体对能量稳态控制做出了贡献。然而，大多数LepRb群体的功能仍不清楚，它们在调节能量动态平衡中的作用也没有被研究过。甘丙肽被假设与瘦素信号系统相互作用，但研究LepRb和甘丙肽共定位的文献一直不一致，这可能是由于技术上的困难来可视化两者。我们使用报告小鼠从甘丙素基因座表达绿色荧光蛋白来概括甘丙素和瘦素诱导的p-STAT3的共存作为LepRb表达的标记。在这里，我们报道了两类表达Galanin的LepRb神经元(Gal-LepRb神经元)：横跨穹隆周围区的下丘脑及其邻近的背内侧和下丘脑外侧区[统称为扩展穹隆周区(Extended Perfornical Area，exPFA)]和脑干(孤束核)。令人惊讶的是，尽管瘦素具有促厌食性甘丙素的作用，但它能诱导exPFA中甘丙素mRNA的表达并刺激LepRb神经元，从而与预期的厌食性瘦素作用相冲突。然而，我们证实，ExPFA内注射瘦素确实足以调节厌食反应。有趣的是，表达LepRb和Galanin的神经元不同于表达增食欲素或黑色素浓缩激素(MCH)的神经元，但ExPFA Galanin神经元与厌食神经肽神经降压素和可卡因和苯丙胺调节转录物(CART)共存。根据甘丙肽已知的抑制功能，我们推测甘丙素在exPFA的Gal-LepRb神经元中起抑制作用，而不是促食欲。
Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions. LepRb neurons are found throughout the brain, and several distinct populations contribute to energy homeostasis control. However, the function of most LepRb populations remains unknown, and their contribution to regulate energy homeostasis has not been studied. Galanin has been hypothesized to interact with the leptin signaling system, but literature investigating colocalization of LepRb and galanin has been inconsistent, which is likely due to technical difficulties to visualize both. We used reporter mice with green fluorescent protein expression from the galanin locus to recapitulate the colocalization of galanin and leptin-induced p-STAT3 as a marker for LepRb expression. Here, we report the existence of two populations of galanin-expressing LepRb neurons (Gal-LepRb neurons): in the hypothalamus overspanning the perifornical area and adjacent dorsomedial and lateral hypothalamus [collectively named extended perifornical area (exPFA)] and in the brainstem (nucleus of the solitary tract). Surprisingly, despite the known orexigenic galanin action, leptin induces galanin mRNA expression and stimulates LepRb neurons in the exPFA, thus conflicting with the expected anorexigenic leptin action. However, we confirmed that intra-exPFA leptin injections were indeed sufficient to mediate anorexic responses. Interestingly, LepRb and galanin-expressing neurons are distinct from orexin or melanin-concentrating hormone (MCH)-expressing neurons, but exPFA galanin neurons colocalized with the anorexigenic neuropeptides neurotensin and cocaine-and amphetamine-regulated transcript (CART). Based on galanin's known inhibitory function, we speculate that in exPFA Gal-LepRb neurons galanin acts inhibitory rather than orexigenic.