Sex-specific metabolic alterations in the type 1 diabetic brain of mice revealed by an integrated method of metabolomics and mixed-model
Sex-specific metabolic alterations in the type 1 diabetic brain of mice revealed by an integrated method of metabolomics and mixed-model
复制标题
代谢组学和混合模型的综合方法揭示了 1 型糖尿病小鼠大脑中性别特异性代谢变化
DOI：
10.1016/j.csbj.2020.07.019
复制
发表时间：
2020-01-01
影响因子：
6
通讯作者：
Zheng, Hong
中科院分区：
文献类型：
--
作者：
Jiang, Qiaoying;Xu, Hangying;Zheng, Hong
1型糖尿病（T1D）可引起脑区域特异性代谢紊乱，但性别是否影响T1D相关的脑代谢改变的报道很少。因此，本研究采用基于NMR的代谢组学和线性混合模型相结合的方法，研究了正常和T1D条件下雄性和雌性小鼠6个不同脑区的代谢变化，旨在探索从正常到T1D的性别特异性代谢变化。结果表明，两种性别之间的所有脑区的代谢差异，而海马代谢更容易受到T1D的影响。治疗后4周，雌性T1D小鼠脑代谢紊乱主要发生在皮质和海马，雄性T1D小鼠主要发生在纹状体和海马。此外，无氧糖酵解在雄性小鼠中显著改变，主要在纹状体、中脑、下丘脑和海马中，但在雌性小鼠中没有改变。我们还发现，从正常到T1D，雌性小鼠相对于雄性小鼠表现出代谢低下状态。总的来说，这项研究表明，T1D以性别特异性的方式影响大脑区域特异性的代谢改变，并可能提供性别之间糖尿病脑疾病的代谢观点。(C)2020作者（S）由Elsevier B.V.代表计算和结构生物技术研究网络出版。
Type 1 diabetes (T1D) can cause brain region-specific metabolic disorders, but whether gender influences T1D-related brain metabolic changes is rarely reported. Therefore, here we examined metabolic changes in six different brain regions of male and female mice under normal and T1D conditions using an integrated method of NMR-based metabolomics and linear mixed-model, and aimed to explore sex-specific metabolic changes from normal to T1D. The results demonstrate that metabolic differences occurred in all brain regions between two genders, while the hippocampal metabolism is more likely to be affected by T1D. At the 4th week after streptozotocin treatment, brain metabolic disorders mainly occurred in the cortex and hippocampus in female T1D mice, but the striatum and hippocampus in male T1D mice. In addition, anaerobic glycolysis was significantly altered in male mice, mainly in the striatum, midbrain, hypothalamus and hippocampus, but not in female mice. We also found that female mice exhibited a hypometabolism status relative to male mice from normal to T1D. Collectively, this study suggests that T1D affected brain region-specific metabolic alterations in a sex-specific manner, and may provide a metabolic view on diabetic brain diseases between genders. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.