Proopiomelanocortin (POMC) neurons contribute to the regulation of many physiologic processes; the majority of which have been attributed to the release of peptides produced from the POMC pro-hormone such as alpha-MSH, which plays key roles in food intake and metabolism. However, it is now clear that POMC neurons also release amino acid (AA) transmitters that likely contribute to the overall function of POMC cells. Recent work indicates that constitutive deletion of these transmitters can affect metabolic phenotypes, but also that the expression of GABAergic or glutamatergic markers changes throughout development. The goal of the present study was to determine if the release of glutamate or GABA from POMC neurons in the adult mouse contributes notably to energy balance regulation. Disturbed release of glutamate or GABA from POMC neurons in adult mice was achieved using a tamoxifen-inducible Cre construct (Pomc-CreER^T2) expressed in mice also carrying floxed versions of Slc17a6 (vGlut2) or Gad1 and Gad2, encoding the vesicular glutamate type 2 and GAD67 and 65 proteins, respectively. All mice received tamoxifen injections, but control mice lacked the inducible Cre sequence. Bodyweight, glucose tolerance and re-feeding after an overnight fast were all unchanged by the disruption of AA transmitter release. These data collectively suggest that the release of GABA or glutamate from POMC neurons in adult mice does not significantly contribute to the metabolic parameters tested here. In light of prior work, it appears that AA transmitter release from POMC cells contributes to separate functions in the adult versus the developing mouse.

中文翻译：

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成年小鼠 POMC 神经元中 GABA 或谷氨酸释放的中断不会影响代谢终点。

阿黑皮素原 (POMC) 神经元有助于调节许多生理过程；其中大部分归因于 POMC 激素原产生的肽的释放，例如 α-MSH，它在食物摄入和代谢中起着关键作用。然而，现在很清楚 POMC 神经元也会释放氨基酸 (AA) 递质，这可能有助于 POMC 细胞的整体功能。最近的工作表明，这些递质的组成性缺失会影响代谢表型，而且 GABA 能或谷氨酸能标记的表达在整个发育过程中都会发生变化。本研究的目的是确定成年小鼠 POMC 神经元中谷氨酸盐或 GABA 的释放是否对能量平衡调节有显着贡献。^T2 ) 在小鼠中表达，也携带 Floxed 版本的 Slc17a6 (vGlut2) 或 Gad1 和 Gad2，分别编码 2 型囊泡谷氨酸和 GAD67 和 65 蛋白。所有小鼠都接受了他莫昔芬注射，但对照小鼠缺乏可诱导的 Cre 序列。体重、葡萄糖耐量和隔夜禁食后的重新进食都因 AA 发射器释放的中断而没有改变。这些数据共同表明，成年小鼠 POMC 神经元中 GABA 或谷氨酸的释放对此处测试的代谢参数没有显着影响。根据先前的工作，似乎从 POMC 细胞中释放的 AA 递质有助于成年小鼠与发育中的小鼠的不同功能。