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- Title
Obesity and hyperglycemia lead to impaired post-ischemic recovery after permanent ischemia in mice.
- Authors
Tulsulkar, Jatin; Nada, Shadia E.; Slotterbeck, Brandon D.; McInerney, Marcia F.; Shah, Zahoor A.
- Abstract
<bold>Objective: </bold>Obesity-induced diabetes has increased over the years and has become one of the risk factors for stroke. We investigated the influence of diet-induced obesity and hyperglycemia on permanent distal middle cerebral artery occlusion (pMCAO)-induced ischemic stroke in mice.<bold>Methods: </bold>Male C57/Bl6 mice were treated with a high-fat/high-carbohydrate diet [HFCD/obese and hyperglycemia (O/H)] or a normal diet (control) for 3.5 months, subjected to pMCAO, and sacrificed after 7 days.<bold>Results: </bold>Infarct volume analysis showed no differences between the O/H and control group, whereas neurological deficits were significantly higher in the O/H group compared to the control group. Sirtuin (Sirt1) was overexpressed and NADPH oxidase was reduced in the O/H group. O/H mice had significantly lower expression of Wnt and glycogen synthase kinase 3 α and β, a key component in the Wnt signaling pathway. Translocation of apoptosis inducing factor (AIF) to the nucleus was observed in both the O/H and control groups, but O/H mice showed a higher expression of AIF in the nucleus.<bold>Conclusions: </bold>These data suggest that impaired Wnt signaling and active apoptosis result in reduced post-stroke recovery in obese and hyperglycemic mice.
- Subjects
DIABETES risk factors; ANIMAL models of ischemia; OBESE-hyperglycemic syndrome; OBESITY complications; NUTRITIONALLY induced diseases; GENE expression in mammals; ANIMAL models in research; ANIMAL experimentation; BIOLOGICAL models; CELLULAR signal transduction; CEREBRAL ischemia; HYPERGLYCEMIA; INFARCTION; MICE; OBESITY; RESEARCH funding; TRANSFERASES
- Publication
Obesity (19307381), 2016, Vol 24, Issue 2, p417
- ISSN
1930-7381
- Publication type
journal article
- DOI
10.1002/oby.21388