Sex-specific metabolic alterations in the type 1 diabetic brain of mice revealed by an integrated method of metabolomics and mixed-model.

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.