Nuclear magnetic resonance spectroscopy reveals biomarkers of stroke recovery in a mouse model of obesity-associated type 2 diabetes

Abstract

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.

Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications

“…Prior research has indicated a significant association between T2D and circulating amino acids ( 18 – 20 ).…”

“…Furthermore, the majority of these studies did not systematically and comprehensively present the associations. For instance, some studies merely compared amino acid profiles without exploring their correlations with diabetes ( 18 , 19 ), while others had a limited number of participants ( 20 ). Previous studies also identified various amino acids that may be strongly linked to T2D.…”

“…The previous studies have underscored the significance of amino acids in diabetes; however, some of them merely compared amino acid profiles without delving into their association with diabetes ( 18 , 19 ).…”