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

Vieira, Joao P.P. LU ; Karampatsi, Dimitra ; Vercalsteren, Ellen ; Darsalia, Vladimer LU ; Patrone, Cesare and Duarte, Joao M.N. LU orcid (2024) In Bioscience Reports 44(7). p.1-10
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... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bioscience Reports
volume
44
issue
7
pages
10 pages
publisher
Portland Press
external identifiers
  • scopus:85200110806
  • pmid:38864508
ISSN
0144-8463
DOI
10.1042/BSR20240249
language
English
LU publication?
yes
id
c9f8dea6-1f6c-460e-884f-32600c069903
date added to LUP
2024-09-23 13:50:53
date last changed
2024-09-24 03:00:03
@article{c9f8dea6-1f6c-460e-884f-32600c069903,
  abstract     = {{<p>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.</p>}},
  author       = {{Vieira, Joao P.P. and Karampatsi, Dimitra and Vercalsteren, Ellen and Darsalia, Vladimer and Patrone, Cesare and Duarte, Joao M.N.}},
  issn         = {{0144-8463}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1--10}},
  publisher    = {{Portland Press}},
  series       = {{Bioscience Reports}},
  title        = {{Nuclear magnetic resonance spectroscopy reveals biomarkers of stroke recovery in a mouse model of obesity-associated type 2 diabetes}},
  url          = {{http://dx.doi.org/10.1042/BSR20240249}},
  doi          = {{10.1042/BSR20240249}},
  volume       = {{44}},
  year         = {{2024}},
}