Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate
Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate
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DOI：
10.1177/0271678x15613955
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发表时间：
2016-10-01
影响因子：
6.3
通讯作者：
Felipe Barros, L.
中科院分区：
文献类型：
--
作者：
Valdebenito, Rocio;Ruminot, Ivan;Felipe Barros, L.
生酮饮食和间歇性禁食对神经系统疾病的有效性引起了人们对酮体对脑细胞影响的兴趣。已知这些化合物可以改变神经元的代谢，但对它们对星形胶质细胞的影响知之甚少，星形胶质细胞控制向神经元供应葡萄糖，并通过乳酸的糖酵解产生来调节神经元的兴奋性。在这里，我们使用了遗传编码的葡萄糖，丙酮酸和ATP的福斯特共振能量转移纳米传感器，以细胞分辨率表征星形胶质细胞的能量代谢。我们的研究结果表明，酮体β-羟基丁酸酯强烈抑制星形胶质细胞在混合培养的小鼠星形胶质细胞中的葡萄糖消耗，在器官型海马切片和从酮症小鼠制备的急性海马切片中，同时钝化由生理和病理生理刺激引起的糖酵解刺激。糖酵解的抑制被星形胶质细胞线粒体代谢丙酮酸的能力增加所抵消。这些结果支持星形胶质细胞有助于酮体的神经保护作用的新概念。
The effectiveness of ketogenic diets and intermittent fasting against neurological disorders has brought interest to the effects of ketone bodies on brain cells. These compounds are known to modify the metabolism of neurons, but little is known about their effect on astrocytes, cells that control the supply of glucose to neurons and also modulate neuronal excitability through the glycolytic production of lactate. Here we have used genetically-encoded Forster Resonance Energy Transfer nanosensors for glucose, pyruvate and ATP to characterize astrocytic energy metabolism at cellular resolution. Our results show that the ketone body beta-hydroxybutyrate strongly inhibited astrocytic glucose consumption in mouse astrocytes in mixed cultures, in organotypic hippocampal slices and in acute hippocampal slices prepared from ketotic mice, while blunting the stimulation of glycolysis by physiological and pathophysiological stimuli. The inhibition of glycolysis was paralleled by an increased ability of astrocytic mitochondria to metabolize pyruvate. These results support the emerging notion that astrocytes contribute to the neuroprotective effect of ketone bodies.