Alterations in brain glucose utilization accompanying elevations in blood ethanol and acetate concentrations in the rat.
Alterations in brain glucose utilization accompanying elevations in blood ethanol and acetate concentrations in the rat.
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DOI：
10.1111/j.1530-0277.2009.01099.x
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Veech RL
中科院分区：
文献类型：
--
作者：
Pawlosky RJ;Kashiwaya Y;Srivastava S;King MT;Crutchfield C;Volkow N;Kunos G;Li TK;Veech RL
先前对人类的研究表明，饮酒会降低大脑葡萄糖的利用率。我们研究了乙醇的主要代谢物乙酸盐是否可以通过提供葡萄糖的替代物作为大脑的能量底物以及这种转变的代谢后果来解释这一观察结果。给大鼠输注含有 13C-2-葡萄糖作为示踪剂的乙酸钠、乙醇或盐水溶液，以提高血液乙醇 (BEC) 和血液乙酸盐 (BAcC) 浓度。一小时后，采集血液样本并通过冷冻吹除法取出动物的大脑。分析组织样本中的葡萄糖代谢中间体、克雷布斯循环、酰基辅酶 A (CoA) 化合物和氨基酸。在注射乙醇的动物中，BEC 和 BAcC 的平均峰值分别约为 25 和 0.8 mM。在注射醋酸盐的动物中，血液 BAcC 峰值增加至 12 mM。与对照组相比，注射乙醇和醋酸盐的动物大脑中对 13C-葡萄糖的摄取较低，并且大脑中 13C-葡萄糖-6-磷酸的浓度与 BAcC 成反比。与盐水对照组相比，乙醇处理的动物脑内丙二酰辅酶 A 浓度较高，游离 Mg2+ 水平较低。在注射醋酸盐的动物中，脑乳酸、α-酮戊二酸和富马酸的浓度较高。此外，游离胞质[NAD+]/[NADH]较低，游离线粒体[NAD+]/[NADH]和[CoQ]/[CoQH2]被氧化，并且乙酸盐输注将ATP的ΔG'从-61.4 kJ降低至-59.9 kJ/mol。血液中乙醇或醋酸盐水平升高的动物大脑对 13C-葡萄糖的摄取减少。在注射醋酸盐的动物中，BAcC 升高与 13C-葡萄糖磷酸化降低相关。游离胞质 NAD 的协调减少、线粒体 NAD 和 Q 对的氧化以及 ATP ΔG' 的减少与施用解偶联剂相似，表明脑中乙酸盐的代谢导致线粒体电压依赖性孔的形成。
Previous studies in humans have shown that alcohol consumption decreased the rate of brain glucose utilization. We investigated whether the major metabolite of ethanol, acetate, could account for this observation by providing an alternate to glucose as an energy substrate for brain and the metabolic consequences of that shift. Rats were infused with solutions of sodium acetate, ethanol, or saline containing 13C-2-glucose as a tracer elevating the blood ethanol (BEC) and blood acetate (BAcC) concentrations. After an hour, blood was sampled and the brains of animals were removed by freeze blowing. Tissue samples were analyzed for the intermediates of glucose metabolism, Krebs’ cycle, acyl-coenzyme A (CoA) compounds, and amino acids. Mean peak BEC and BAcC were approximately 25 and 0.8 mM, respectively, in ethanol-infused animals. Peak blood BAcC increased to 12 mM in acetate-infused animals. Both ethanol and acetate infused animals had a lower uptake of 13C-glucose into the brain compared to controls and the concentration of brain 13C-glucose-6-phosphate varied inversely with the BAcC. There were higher concentrations of brain malonyl-CoA and somewhat lower levels of free Mg2+ in ethanol-treated animals compared to saline controls. In acetate-infused animals the concentrations of brain lactate, α-ketoglutarate, and fumarate were higher. Moreover, the free cytosolic [NAD+]/[NADH] was lower, the free mitochondrial [NAD+]/[NADH] and [CoQ]/[CoQH2] were oxidized and the ΔG′ of ATP lowered by acetate infusion from −61.4 kJ to −59.9 kJ/mol. Animals with elevated levels of blood ethanol or acetate had decreased 13C-glucose uptake into the brain. In acetate-infused animals elevated BAcC were associated with a decrease in 13C-glucose phosphorylation. The co-ordinate decrease in free cytosolic NAD, oxidation of mitochondrial NAD and Q couples and the decrease in ΔG′ of ATP was similar to administration of uncoupling agents indicating that the metabolism of acetate in brain caused the mitochondrial voltage dependent pore to form.
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影响因子：
2.6
作者：
Chen, Yi-Chyan;Peng, Giia-Sheun;Yin, Shih-Jiun
通讯作者：
Yin, Shih-Jiun
DOI：
10.1111/j.1530-0277.1980.tb04833.x
发表时间：
1980-01-01
影响因子：
3.2
作者：
COHEN, G;SINET, PM;HEIKKILA, R
通讯作者：
HEIKKILA, R
影响因子：
4.7
作者：
VEECH, RL;HARRIS, RL;VEECH, EH
通讯作者：
VEECH, EH
影响因子：
4.7
作者：
Deelchand DK;Shestov AA;Koski DM;Uğurbil K;Henry PG
通讯作者：
Henry PG
影响因子：
7.4
作者：
Soga, T;Ueno, Y;Nishioka, T
通讯作者：
Nishioka, T