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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate
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Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate

机译：β-羟基丁酸酯靶向星形细胞葡萄糖代谢

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摘要

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.
机译：生酮饮食和针对神经系统疾病的间歇性禁食的有效性引起了对酮体对脑细胞的影响的兴趣。已知这些化合物可改变神经元的代谢，但对星形胶质细胞（控制葡萄糖向神经元的供给并通过乳酸的糖酵解产生来调节神经元兴奋性）的细胞的作用知之甚少。在这里，我们已使用遗传编码的Forster共振能量转移纳米传感器检测葡萄糖，丙酮酸和ATP，以细胞分辨率表征星形细胞能量代谢。我们的结果表明，酮体β-羟基丁酸酯强烈抑制混合培养物中，星形胶质小鼠制备的器官型海马切片和急性海马切片中小鼠星形胶质细胞中星形胶质糖的消耗，同时减弱了生理和病理生理刺激对糖酵解的刺激。糖酵解的抑制作用与星形细胞线粒体代谢丙酮酸的能力增强相平行。这些结果支持了新出现的观念，即星形胶质细胞有助于酮体的神经保护作用。

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