Activation of Agouti-Related Peptide (AgRP)-expressing neurons promotes feeding and insulin resistance. Here, we examine the contribution of neuropeptide Y (NPY)-dependent signaling to the diverse physiological consequences of activating AgRP neurons. NPY-deficient mice fail to rapidly increase food intake during the first hour of either chemo- or optogenetic activation of AgRP neurons, while the delayed increase in feeding is comparable between control and NPY-deficient mice. Acutely stimulating AgRP neurons fails to induce systemic insulin resistance in NPY-deficient mice, while increased locomotor activity upon AgRP neuron stimulation in the absence of food remains unaffected in these animals. Selective re-expression of NPY in AgRP neurons attenuates the reduced feeding response and reverses the protection from insulin resistance upon optogenetic activation of AgRP neurons in NPY-deficient mice. Collectively, these experiments reveal a pivotal role of NPY-dependent signaling in mediating the rapid feeding inducing effect and the acute glucose regulatory function governed by AgRP neurons.

中文翻译：

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NPY介导AgRP神经元的快速进食和葡萄糖代谢调节功能。

表达刺痛相关肽（AgRP）的神经元的激活促进进食和胰岛素抵抗。在这里，我们检查了神经肽Y（NPY）依赖信号对激活AgRP神经元的各种生理后果的贡献。NPY缺陷小鼠在AgRP神经元化学激活或光遗传激活的第一个小时内无法快速增加食物摄入量，而延迟喂养的增加与对照组和NPY缺陷小鼠相当。急性刺激AgRP神经元不能诱导NPY缺陷小鼠全身性胰岛素抵抗，而在缺乏食物的情况下，AgRP神经元刺激后运动能力的增强在这些动物中仍不受影响。在NPY缺陷小鼠中，AgRP神经元的光遗传激活后，AgRP神经元中NPY的选择性重新表达减弱了降低的进食反应，并逆转了对胰岛素抵抗的保护作用。总之，这些实验揭示了NPY依赖性信号传导在介导由AgRP神经元控制的快速进食诱导作用和急性葡萄糖调节功能中的关键作用。