Diabetes and Brain Function Unit, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, Sweden.
Wallenberg Centre for Molecular Medicine, Lund University, 221 84 Lund, Sweden.
Biosci Rep. 2024 Jul 31;44(7). doi: 10.1042/BSR20240249.
Obesity and Type 2 diabetes (T2D) are known to exacerbate cerebral injury caused by stroke. Metabolomics can provide signatures of metabolic disease, and now we explored whether the analysis of plasma metabolites carries biomarkers of how obesity and T2D impact post-stroke recovery. Male mice were fed a high-fat diet (HFD) for 10 months leading to development of obesity with T2D or a standard diet (non-diabetic mice). Then, mice were subjected to either transient middle cerebral artery occlusion (tMCAO) or sham surgery and allowed to recover on standard diet for 2 months before serum samples were collected. Nuclear magnetic resonance (NMR) spectroscopy of serum samples was used to investigate metabolite signals and metabolic pathways that were associated with tMCAO recovery in either T2D or non-diabetic mice. Overall, after post-stroke recovery there were different serum metabolite profiles in T2D and non-diabetic mice. In non-diabetic mice, which show full neurological recovery after stroke, we observed a reduction of isovalerate, and an increase of kynurenate, uridine monophosphate, gluconate and N6-acetyllysine in tMCAO relative to sham mice. In contrast, in mice with T2D, which show impaired stroke recovery, there was a reduction of N,N-dimethylglycine, succinate and proline, and an increase of 2-oxocaproate in serum of tMCAO versus sham mice. Given the inability of T2D mice to recover from stroke, in contrast with non-diabetic mice, we propose that these specific metabolite changes following tMCAO might be used as biomarkers of neurophysiological recovery after stroke in T2D.
肥胖和 2 型糖尿病（T2D）已知会加重中风引起的脑损伤。代谢组学可以提供代谢疾病的特征，现在我们探讨了分析血浆代谢物是否携带肥胖和 T2D 影响中风后恢复的生物标志物。雄性小鼠喂食高脂肪饮食（HFD）10 个月，导致肥胖伴 T2D 或标准饮食（非糖尿病小鼠）。然后，将小鼠进行短暂性大脑中动脉闭塞（tMCAO）或假手术，并在标准饮食上恢复 2 个月，然后收集血清样本。使用核磁共振（NMR）光谱分析血清样本，以研究与 tMCAO 恢复相关的代谢物信号和代谢途径，无论是在 T2D 还是非糖尿病小鼠中。总的来说，中风后恢复后，T2D 和非糖尿病小鼠的血清代谢谱不同。在非糖尿病小鼠中，中风后完全恢复神经功能，我们观察到异戊酸盐减少，而色氨酸、尿苷一磷酸、葡萄糖酸盐和 N6-乙酰赖氨酸增加。相比之下，在 T2D 小鼠中，中风恢复受损，tMCAO 与假手术相比，N,N-二甲基甘氨酸、琥珀酸和脯氨酸减少，2-氧代己酸增加。鉴于 T2D 小鼠不能从中风中恢复，与非糖尿病小鼠相反，我们提出，tMCAO 后这些特定的代谢物变化可能被用作 T2D 中风后神经生理恢复的生物标志物。
