Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France.
Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA; Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, GA 30302, USA.
Cell Metab. 2022 Oct 4;34(10):1532-1547.e6. doi: 10.1016/j.cmet.2022.09.002.
The hypothalamus is key in the control of energy balance. However, strategies targeting hypothalamic neurons have failed to provide viable options to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored. Here, we show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus (PVN) of the hypothalamus, chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism, and energy balance. This process recruits a mechanism involving the astrocytic control of ambient glutamate levels, which becomes defective in obesity. Positive or negative chemogenetic manipulation of PVN astrocyte Ca signals, respectively, worsens or improves metabolic status of diet-induced obese mice. Collectively, these findings highlight a yet unappreciated role for astrocytes in the direct control of systemic metabolism and suggest potential targets for anti-obesity strategy.
下丘脑在能量平衡的控制中起着关键作用。然而，针对下丘脑神经元的策略未能为大多数代谢疾病提供可行的治疗选择。相反，星形胶质细胞在全身代谢控制中的作用在很大程度上仍未得到探索。在这里，我们表明肥胖促进了下丘脑星形胶质细胞活动的解剖限制重塑。在下丘脑室旁核（PVN）中，星形胶质细胞的化学遗传操作导致相邻神经元活动、自主神经输出、葡萄糖代谢和能量平衡的双向控制。这个过程涉及到一个机制，即星形胶质细胞控制环境中谷氨酸水平，而肥胖会使其失去功能。PVN 星形胶质细胞 Ca 信号的正或负化学遗传操作分别使饮食诱导肥胖小鼠的代谢状况恶化或改善。总的来说，这些发现强调了星形胶质细胞在直接控制全身代谢中的作用，为抗肥胖策略提供了潜在的靶点。
