Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Diabetes. 2024 Dec 1;73(12):1942-1951. doi: 10.2337/dbi24-0002.
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.
弓状核前阿黑皮素原（POMC）神经元活性增加可改善葡萄糖代谢并减少食欲，从而促进体重减轻。我们最近发现，运动可激活弓状核 POMC 神经元。然而，兴奋性谷氨酸能传入在这些神经元中的作用以及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 NMDA 受体（NMDARs）选择性缺失成年小鼠弓状核 POMC 神经元的小鼠模型。我们进行了代谢评估，包括监测体重、身体成分分析和葡萄糖代谢耐量试验。我们还研究了这些小鼠对运动的代谢反应，包括弓状核 POMC 神经元活性和胰岛素敏感性的变化。POMC 神经元中 NMDAR 的缺失并未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明显受损。此外，运动导致弓状核 POMC 神经元激活，并持续改善胰岛素敏感性，而与相应的久坐对照组相比，POMC 神经元中 NMDAR 缺失的小鼠则消除了这种作用。这突显了运动、下丘脑神经元功能和代谢健康之间的重要联系。此外，这凸显了下丘脑 POMC 神经元在介导运动对葡萄糖代谢的有益影响方面的作用被低估。
