Jiang Qiaoying, Xu Hangying, Yan Junjie, Xu Qingqing, Zheng Yafei, Li Chen, Zhao Liangcai, Gao Hongchang, Zheng Hong
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Comput Struct Biotechnol J. 2020 Jul 31;18:2063-2074. doi: 10.1016/j.csbj.2020.07.019. eCollection 2020.
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.
1型糖尿病（T1D）可导致脑区特异性代谢紊乱，但性别是否会影响与T1D相关的脑代谢变化鲜有报道。因此，我们在此使用基于核磁共振的代谢组学和线性混合模型的综合方法，研究了正常和T1D条件下雄性和雌性小鼠六个不同脑区的代谢变化，旨在探索从正常状态到T1D状态下的性别特异性代谢变化。结果表明，两性所有脑区均存在代谢差异，而海马体代谢更易受到T1D的影响。链脲佐菌素治疗后第4周，雌性T1D小鼠的脑代谢紊乱主要发生在皮层和海马体，而雄性T1D小鼠则发生在纹状体和海马体。此外，雄性小鼠的无氧糖酵解显著改变，主要发生在纹状体、中脑、下丘脑和海马体，而雌性小鼠则未出现这种情况。我们还发现，从正常状态到T1D状态，雌性小鼠相对于雄性小鼠呈现低代谢状态。总体而言，本研究表明T1D以性别特异性方式影响脑区特异性代谢改变，并可能为两性糖尿病脑病提供代谢方面的见解。
