Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes
Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes
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DOI：
10.1172/jci64102
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发表时间：
2012-11-01
影响因子：
15.9
通讯作者：
Chowen, Julie A.
中科院分区：
文献类型：
--
作者：
Fuente-Martin, Esther;Garcia-Caceres, Cristina;Chowen, Julie A.
神经胶质细胞执行改变神经元代谢和活动的关键功能，并且人们对其在食欲和能量平衡中的作用越来越感兴趣。瘦素是食欲和新陈代谢的关键调节剂，此前已被报道可影响神经胶质结构蛋白和形态。在这里，我们证明代谢状态和瘦素也会改变星形胶质细胞特异性谷氨酸和葡萄糖转运蛋白，表明代谢信号影响突触功效和葡萄糖摄取，并最终影响神经元功能。我们发现，在喂食高脂肪饮食的母亲的后代中，小鼠下丘脑阿黑皮质素原 (POMC) 神经元的基础和葡萄糖刺激的电活动发生了改变。在成年期，体重增加和禁食也会改变葡萄糖和谷氨酸转运蛋白的表达。这些结果表明，整个生物体代谢改变了下丘脑神经胶质细胞的活性，并表明这些细胞在肥胖病理学中发挥着重要作用。
Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity.