The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo
The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo
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DOI：
10.1038/jcbfm.2014.77
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发表时间：
2014-07-01
影响因子：
6.3
通讯作者：
Behar, Kevin L.
中科院分区：
文献类型：
--
作者：
Chowdhury, Golam M. I.;Jiang, Lihong;Behar, Kevin L.
酮体取代葡萄糖支持神经元功能的能力尚不清楚。在这里，我们测定了葡萄糖和酮体在大范围脑活动中对大鼠新皮质氧化代谢的贡献，禁食36小时并静脉注射[2,4- c -13(2)]- d - β -羟基丁酸酯（BHB）。研究了三种动物组和条件：清醒的离体、戊巴比妥诱导的离体等电和氟烷麻醉的离体，并对后者的数据进行了重新分析。通过对脑内主要氨基酸库中C-13标记物的代谢建模，研究了酮体（VaccoA-kbN）和丙酮酸（V-pdhN）对神经元乙酰辅酶a的氧化速率以及谷氨酸-谷氨酰胺循环（V-cyc）。与三羧酸（TCA）循环率（V-tcaN）的急剧变化相比，VacCoA-kbN随着活性的增加而逐渐增加，支持神经元酮氧化百分比的下降：在我们的实验中（6至13 mM） BHB血浆水平接近100%（等电），56%（氟烷麻醉），36%（清醒）。在清醒的动物中，酮氧化达到血中饱和水平bbb17mm，占神经元底物氧化的62%，其余的（38% /o）由葡萄糖提供。我们得出的结论是，酮体存在于足够的浓度以饱和代谢，提供了基础（内源性）能量需求的充分支持，以及大约一半的神经元活动依赖的氧化需求。
The capacity of ketone bodies to replace glucose in support of neuronal function is unresolved. Here, we determined the contributions of glucose and ketone bodies to neocortical oxidative Metabolism over a large range of brain activity in rats fasted 36 hours and infused intravenously with [2,4-C-13(2)]-D-beta-hydroxybutyrate (BHB). Three animal groups and conditions were studied: awake ex vivo, pentobarbital-induced isoelectricity ex vivo, and halothane-anesthetized in vivo, the latter data reanalyzed from a recent study. Rates of neuronal acetyl-CoA oxidation from ketone bodies (VaccoA-kbN) and pyruvate (V-pdhN), and the glutamate-glutamine cycle (V-cyc) were determined by metabolic modeling of C-13 label trapped in major brain amino acid pools. VacCoA-kbN increased gradually with increasing activity, as compared with the steeper change in tricarboxylic acid (TCA) cycle rate (V-tcaN), supporting a decreasing percentage of neuronal ketone oxidation: similar to 100% (isoelectricity), 56% (halothane anesthesia), 36% (awake) with the BHB plasma levels achieved in our experiments (6 to 13 mM). In awake animals ketone oxidation reached saturation for blood levels > 17 mM, accounting for 62% of neuronal substrate oxidation, the remainder (38 /o) provided by glucose. We conclude that ketone bodies present at sufficient concentration to saturate metabolism provides full support of basal (housekeeping) energy needs and up to approximately half Of the activity-dependent oxidative needs of neurons.