The components required for amino acid neurotransmitter signaling are present in adipose tissues
The components required for amino acid neurotransmitter signaling are present in adipose tissues
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DOI：
10.1194/jlr.m700021-jlr200
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发表时间：
2007-10-01
影响因子：
6.5
通讯作者：
Iversen, Per Ole
中科院分区：
文献类型：
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作者：
Nicolaysen, Anne;Gammelsaeter, Runhild;Iversen, Per Ole
脂肪细胞不仅作为燃料储存，而且产生和分泌对食物摄入和能量稳态具有调节作用的化合物。虽然有确凿的证据表明，通过自主神经系统的脂肪细胞功能的中枢介导的调节，很少有人知道脂肪细胞之间的信号。氨基酸神经递质是这种旁分泌信号的候选者。在这里，我们应用免疫组织化学检测大鼠脂肪库中氨基酸递质信号传导所需的组分。在肩胛间棕色脂肪组织以及肩胛间、肠系膜、肾周和附睾白色脂肪组织中，我们证明了兴奋性神经递质谷氨酸、抑制性神经递质γ-氨基丁酸（GABA）和GABA合成酶谷氨酸脱羧酶（GAD）亚型GAD 65和GAD 67的强大免疫信号。此外，除了囊泡标记物突触素外，所有脂肪组织均对囊泡谷氨酸转运体VGLUT 1和囊泡GABA转运体VGAT进行染色。电镜免疫细胞化学显示，VGLUT 1和VGAT，而不是VGLUT 2或VGLUT 3，定位于囊泡细胞器中的脂肪细胞。脂肪细胞中存在谷氨酸受体（亚基GluR 2/3和NR 1，但不含mGluR 2）和GABA受体（GABA（A）R α 2）。谷氨酸、GABA、它们的囊泡转运体和它们的受体的存在表明脂肪组织中氨基酸的旁分泌信号作用。
The adipocyte does not only serve as fuel storage but produces and secretes compounds with modulating effects on food intake and energy homeostasis. Although there is firm evidence for a centrally mediated regulation of adipocyte function via the autonomous nervous system, little is known about signaling between adipocytes. Amino acid neurotransmitters are candidates for such paracrine signaling. Here, we applied immunohistochemistry to detect components required for amino acid transmitter signaling in rat fat depots. In interscapular brown adipose tissue as well as in interscapular, mesenteric, perirenal, and epididymal white adipose tissues, we demonstrate robust immunosignals for the excitatory neurotransmitter glutamate, the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and the GABA-synthesizing enzyme glutamate decarboxylase (GAD) isoforms GAD65 and GAD67. Moreover, all adipose tissues stained for the vesicular glutamate transporter VGLUT1 and the vesicular GABA transporter VGAT in addition to the vesicle marker synaptophysin. Electron microscopic immunocytochemistry showed that VGLUT1 and VGAT, but not VGLUT2 or VGLUT3, are localized in vesicular organelles in adipocytes. The receptors for glutamate (subunits GluR2/3 and NR1 but not mGluR2) and for GABA (GABA(A)R alpha 2) were present in the adipocytes. The presence of glutamate, GABA, their vesicular transporters, and their receptors indicates a paracrine signaling role for amino acids in adipose tissues.