Increased arcuate proopiomelanocortin (POMC) neuron activity improves glucose metabolism and reduces appetite, facilitating weight loss. We recently showed that arcuate POMC neurons are activated by exercise. However, the role of excitatory glutamatergic input in these neurons and the metabolic outcomes of exercise remains undefined. To investigate this, we developed a mouse model with NMDA receptors (NMDARs) selectively deleted from POMC neurons of adult mice. We performed metabolic assessments, including the monitoring of body weight, body composition analysis, and glucometabolic tolerance tests. We also examined the metabolic outcomes of these mice in response to exercise, including changes in arcuate POMC neuronal activity and insulin sensitivity. Loss of NMDARs in POMC neurons failed to alter body weight or body composition. Notably, however, we did observe a marked impairment in glucose tolerance and insulin sensitivity. Additionally, exercise resulted in activation of arcuate POMC neurons and a sustained improvement in insulin sensitivity, an effect that was abrogated in mice deficient for NMDARs in POMC neurons when compared with their respective sedentary controls. This underscores an important link among exercise, hypothalamic neuron function, and metabolic health. Moreover, this highlights an underappreciated role of hypothalamic POMC neurons in mediating beneficial effects of exercise on glucose metabolism.

中文翻译：

---

POMC 神经元中的 NMDA 受体将运动与胰岛素敏感性联系起来


弓状原黑皮质素 （POMC） 神经元活性增加可改善葡萄糖代谢并降低食欲，促进体重减轻。我们最近表明，弓状 POMC 神经元被运动激活。然而，兴奋性谷氨酸能输入在这些神经元中的作用和运动的代谢结果仍未确定。为了研究这一点，我们开发了一种小鼠模型，其中 NMDA 受体 （NMDARs） 从成年小鼠的 POMC 神经元中选择性删除。我们进行了代谢评估，包括体重监测、身体成分分析和糖代谢耐量试验。我们还检查了这些小鼠对运动的反应代谢结果，包括弓状 POMC 神经元活动和胰岛素敏感性的变化。POMC 神经元中 NMDARs 的缺失未能改变体重或身体成分。然而，值得注意的是，我们确实观察到葡萄糖耐量和胰岛素敏感性的显着损害。此外，运动导致弓状 POMC 神经元的激活和胰岛素敏感性的持续改善，与各自的久坐对照相比，这种影响在 POMC 神经元中缺乏 NMDAR 的小鼠中被消除。这强调了运动、下丘脑神经元功能和代谢健康之间的重要联系。此外，这突出了下丘脑 POMC 神经元在介导运动对葡萄糖代谢的有益影响中被低估的作用。