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Prevention of Metabolic Impairment by Dietary Nitrate in Overweight Male Mice Improves Stroke Outcome

Vercalsteren, Ellen ; Karampatsi, Dimitra ; Buizza, Carolina LU ; Paul, Gesine LU orcid ; Lundberg, Jon O. ; Nyström, Thomas ; Darsalia, Vladimer LU and Patrone, Cesare (2025) In Nutrients 17(15).
Abstract

Background/objectives: Being overweight increases the predisposition to obesity and type 2 diabetes (T2D), which significantly elevate stroke risk and the likelihood of severe post-stroke disability. Dietary nitrate (NO3−) supplementation can mitigate obesity and metabolic impairments, making it a promising approach to halt overweight people from developing overt obesity/T2D, thereby potentially also improving stroke outcome. We determined whether NO3− supplementation prevents overweight mice from progressing into obesity and T2D and whether this intervention improves stroke outcome. Methods: An overweight condition was induced via 6 weeks of a high-fat diet (HFD), after which animals were randomized to... (More)

Background/objectives: Being overweight increases the predisposition to obesity and type 2 diabetes (T2D), which significantly elevate stroke risk and the likelihood of severe post-stroke disability. Dietary nitrate (NO3−) supplementation can mitigate obesity and metabolic impairments, making it a promising approach to halt overweight people from developing overt obesity/T2D, thereby potentially also improving stroke outcome. We determined whether NO3− supplementation prevents overweight mice from progressing into obesity and T2D and whether this intervention improves stroke outcome. Methods: An overweight condition was induced via 6 weeks of a high-fat diet (HFD), after which animals were randomized to either a HFD or a HFD with NO3− supplementation. After 24 weeks, when HFD-mice without NO3− developed obesity and T2D, all animals were subjected to transient middle cerebral artery occlusion and stroke outcome was assessed via behavioral testing and infarct size. The effect of NO3− on post-stroke neuroinflammation, neurogenesis, and neovascularization was analyzed by immunohistochemistry. Results: Sustained NO3− supplementation in overweight mice did not prevent obesity or insulin resistance. However, it attenuated weight gain, prevented hyperglycemia, and significantly improved functional recovery after stroke, without affecting infarct size. Moreover, NO3− decreased post-stroke neuroinflammation by reducing microglial infiltration. NO3− did not affect stroke-induced neurogenesis or vascularization. Conclusion: These results highlight the potential of NO3− supplementation to prevent metabolic impairment in the overweight population and improve stroke prognosis in this large group of people at risk of stroke and severe stroke sequelae.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
diabetes, nitrate, obesity, overweight, stroke
in
Nutrients
volume
17
issue
15
article number
2434
publisher
MDPI AG
external identifiers
  • pmid:40806018
  • scopus:105013292111
ISSN
2072-6643
DOI
10.3390/nu17152434
language
English
LU publication?
yes
id
b48ed6d5-5dda-4320-b704-ed2a88b49cc0
date added to LUP
2025-11-10 12:47:52
date last changed
2025-12-08 20:01:51
@article{b48ed6d5-5dda-4320-b704-ed2a88b49cc0,
  abstract     = {{<p>Background/objectives: Being overweight increases the predisposition to obesity and type 2 diabetes (T2D), which significantly elevate stroke risk and the likelihood of severe post-stroke disability. Dietary nitrate (NO<sub>3</sub><sup>−</sup>) supplementation can mitigate obesity and metabolic impairments, making it a promising approach to halt overweight people from developing overt obesity/T2D, thereby potentially also improving stroke outcome. We determined whether NO3<sup>−</sup> supplementation prevents overweight mice from progressing into obesity and T2D and whether this intervention improves stroke outcome. Methods: An overweight condition was induced via 6 weeks of a high-fat diet (HFD), after which animals were randomized to either a HFD or a HFD with NO<sub>3</sub><sup>−</sup> supplementation. After 24 weeks, when HFD-mice without NO<sub>3</sub><sup>−</sup> developed obesity and T2D, all animals were subjected to transient middle cerebral artery occlusion and stroke outcome was assessed via behavioral testing and infarct size. The effect of NO<sub>3</sub><sup>−</sup> on post-stroke neuroinflammation, neurogenesis, and neovascularization was analyzed by immunohistochemistry. Results: Sustained NO<sub>3</sub><sup>−</sup> supplementation in overweight mice did not prevent obesity or insulin resistance. However, it attenuated weight gain, prevented hyperglycemia, and significantly improved functional recovery after stroke, without affecting infarct size. Moreover, NO<sub>3</sub><sup>−</sup> decreased post-stroke neuroinflammation by reducing microglial infiltration. NO<sub>3</sub><sup>−</sup> did not affect stroke-induced neurogenesis or vascularization. Conclusion: These results highlight the potential of NO<sub>3</sub><sup>−</sup> supplementation to prevent metabolic impairment in the overweight population and improve stroke prognosis in this large group of people at risk of stroke and severe stroke sequelae.</p>}},
  author       = {{Vercalsteren, Ellen and Karampatsi, Dimitra and Buizza, Carolina and Paul, Gesine and Lundberg, Jon O. and Nyström, Thomas and Darsalia, Vladimer and Patrone, Cesare}},
  issn         = {{2072-6643}},
  keywords     = {{diabetes; nitrate; obesity; overweight; stroke}},
  language     = {{eng}},
  number       = {{15}},
  publisher    = {{MDPI AG}},
  series       = {{Nutrients}},
  title        = {{Prevention of Metabolic Impairment by Dietary Nitrate in Overweight Male Mice Improves Stroke Outcome}},
  url          = {{http://dx.doi.org/10.3390/nu17152434}},
  doi          = {{10.3390/nu17152434}},
  volume       = {{17}},
  year         = {{2025}},
}