Diet-induced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke.
Animals
Behavior, Animal
Biomarkers
/ blood
Blood Glucose
/ metabolism
Brain
/ metabolism
Diabetes Mellitus, Type 2
/ blood
Diet, High-Fat
Disease Models, Animal
Glycemic Control
Infarction, Middle Cerebral Artery
/ blood
Male
Mice, Inbred C57BL
Obesity
/ blood
Recovery of Function
Stroke
/ blood
Time Factors
Weight Loss
Insulin resistance
Neurological recovery
Stroke
Type 2 diabetes
Weight loss
Journal
Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637
Informations de publication
Date de publication:
22 12 2021
22 12 2021
Historique:
received:
07
10
2021
accepted:
02
12
2021
entrez:
23
12
2021
pubmed:
24
12
2021
medline:
22
2
2022
Statut:
epublish
Résumé
Post-stroke functional recovery is severely impaired by type 2 diabetes (T2D). This is an important clinical problem since T2D is one of the most common diseases. Because weight loss-based strategies have been shown to decrease stroke risk in people with T2D, we aimed to investigate whether diet-induced weight loss can also improve post-stroke functional recovery and identify some of the underlying mechanisms. T2D/obesity was induced by 6 months of high-fat diet (HFD). Weight loss was achieved by a short- or long-term dietary change, replacing HFD with standard diet for 2 or 4 months, respectively. Stroke was induced by middle cerebral artery occlusion and post-stroke recovery was assessed by sensorimotor tests. Mechanisms involved in neurovascular damage in the post-stroke recovery phase, i.e. neuroinflammation, impaired angiogenesis and cellular atrophy of GABAergic parvalbumin (PV)+ interneurons were assessed by immunohistochemistry/quantitative microscopy. Both short- and long-term dietary change led to similar weight loss. However, only the latter enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and insulin resistance, and with the reduction of T2D-induced cellular atrophy of PV+ interneurons. Moreover, stroke recovery was associated with decreased T2D-induced neuroinflammation and reduced astrocyte reactivity in the contralateral striatum. The global diabetes epidemic will dramatically increase the number of people in need of post-stroke treatment and care. Our results suggest that diet-induced weight loss leading to pre-stroke normalization of glucose metabolism has great potential to reduce the sequelae of stroke in the diabetic population.
Sections du résumé
BACKGROUND
Post-stroke functional recovery is severely impaired by type 2 diabetes (T2D). This is an important clinical problem since T2D is one of the most common diseases. Because weight loss-based strategies have been shown to decrease stroke risk in people with T2D, we aimed to investigate whether diet-induced weight loss can also improve post-stroke functional recovery and identify some of the underlying mechanisms.
METHODS
T2D/obesity was induced by 6 months of high-fat diet (HFD). Weight loss was achieved by a short- or long-term dietary change, replacing HFD with standard diet for 2 or 4 months, respectively. Stroke was induced by middle cerebral artery occlusion and post-stroke recovery was assessed by sensorimotor tests. Mechanisms involved in neurovascular damage in the post-stroke recovery phase, i.e. neuroinflammation, impaired angiogenesis and cellular atrophy of GABAergic parvalbumin (PV)+ interneurons were assessed by immunohistochemistry/quantitative microscopy.
RESULTS
Both short- and long-term dietary change led to similar weight loss. However, only the latter enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and insulin resistance, and with the reduction of T2D-induced cellular atrophy of PV+ interneurons. Moreover, stroke recovery was associated with decreased T2D-induced neuroinflammation and reduced astrocyte reactivity in the contralateral striatum.
CONCLUSION
The global diabetes epidemic will dramatically increase the number of people in need of post-stroke treatment and care. Our results suggest that diet-induced weight loss leading to pre-stroke normalization of glucose metabolism has great potential to reduce the sequelae of stroke in the diabetic population.
Identifiants
pubmed: 34937562
doi: 10.1186/s12933-021-01426-z
pii: 10.1186/s12933-021-01426-z
pmc: PMC8697500
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
240Subventions
Organisme : Vetenskapsrådet
ID : 2018-02483
Organisme : Vetenskapsrådet
ID : 2017-02255
Informations de copyright
© 2021. The Author(s).
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