Obesity and hyperglycemia lead to impaired post-ischemic recovery after permanent ischemia in mice

Obesity (Silver Spring). 2016 Feb;24(2):417-23. doi: 10.1002/oby.21388. Epub 2015 Dec 23.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: These data suggest that impaired Wnt signaling and active apoptosis result in reduced post-stroke recovery in obese and hyperglycemic mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Ischemia / metabolism*
  • Disease Models, Animal
  • Glycogen Synthase Kinase 3
  • Hyperglycemia / metabolism*
  • Infarction, Middle Cerebral Artery / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / metabolism*
  • Signal Transduction

Substances

  • Glycogen Synthase Kinase 3
  • glycogen synthase kinase 3 alpha