Improved cerebral energetics and ketone body metabolism in db/db mice
Improved cerebral energetics and ketone body metabolism in db/db mice
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DOI：
10.1177/0271678x16684154
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发表时间：
2017-03-01
影响因子：
6.3
通讯作者：
Waagepetersen, Helle S.
中科院分区：
文献类型：
--
作者：
Andersen, Jens V.;Christensen, Sofie K.;Waagepetersen, Helle S.
2型糖尿病是一种常见的糖尿病。2型糖尿病患者大脑替代底物的重要性知之甚少。本研究的目的是调查酮体是否是补偿脑葡萄糖代谢低下的相关候选者，并阐明2型糖尿病脑线粒体的功能。将db/db小鼠急性分离的大脑皮层和海马切片在含有[U-C-13]葡萄糖、[1，2-C-13]乙酸盐或[U-C-13]-羟基丁酸盐的培养基中孵育，并通过质谱法分析组织提取物。海马XFe 96法测定db/db小鼠脑线粒体耗氧量，荧光素酶法测定脑线粒体ATP合成。db/db小鼠的大脑皮质和海马切片均观察到葡萄糖代谢减退。观察到db/db小鼠海马切片中[1，2-C-13]乙酸盐和[U-C-13]-羟基丁酸盐的代谢显著增加。此外，db/db小鼠脑线粒体的耗氧量和ATP合成率升高。这项研究提供了2型糖尿病患者脑能量代谢发生变化的证据。db/db小鼠海马酮体利用增加和线粒体功能改善可能是适应性机制，以维持糖代谢障碍期间的脑能量。
It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate for cerebral glucose hypometabolism and unravel the functionality of cerebral mitochondria in type 2 diabetes mellitus. Acutely isolated cerebral cortical and hippocampal slices of db/db mice were incubated in media containing [U-C-13]glucose, [1,2-C-13]acetate or [U-C-13]-hydroxybutyrate and tissue extracts were analysed by mass spectrometry. Oxygen consumption and ATP synthesis of brain mitochondria of db/db mice were assessed by Seahorse XFe96 and luciferin-luciferase assay, respectively. Glucose hypometabolism was observed for both cerebral cortical and hippocampal slices of db/db mice. Significant increased metabolism of [1,2-C-13]acetate and [U-C-13]-hydroxybutyrate was observed for hippocampal slices of db/db mice. Furthermore, brain mitochondria of db/db mice exhibited elevated oxygen consumption and ATP synthesis rate. This study provides evidence of several changes in brain energy metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism.