Diet-induced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke.

Autor: Karampatsi D; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden., Zabala A; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden., Wilhelmsson U; Laboratory of Astrocyte Biology and CNS Regeneration, Department of Clinical Neuroscience and Rehabilitation, Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden., Dekens D; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden., Vercalsteren E; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden., Larsson M; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden., Nyström T; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden., Pekny M; Laboratory of Astrocyte Biology and CNS Regeneration, Department of Clinical Neuroscience and Rehabilitation, Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden., Patrone C; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden. cesare.patrone@ki.se., Darsalia V; NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden. vladimer.darsalia@ki.se.
Jazyk: angličtina
Zdroj: Cardiovascular diabetology [Cardiovasc Diabetol] 2021 Dec 22; Vol. 20 (1), pp. 240. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1186/s12933-021-01426-z
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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