The detrimental effect of diet-induced obesity on stroke outcome in mice is influenced by the duration of the ischemic insult

Obesity, with increasing prevalence in western societies, positively correlates with an increased riskfor ischemic stroke. We have previously demonstrated that the infarct size and severity of injury issignificantly increased in leptin deficient obese mice (ob/ob)1. Here we used a more translationalmodel to evaluate the effect of long term diet-induced obesity on stroke outcome using a model oftransient ischemic stroke and determined whether the extent of ischaemia influenced outcome2.Male C57BL/6 mice were maintained on either a high-fat (HFD, 60%-fat) or control (12%-fat)] dietfor 28�2 weeks. Blood pressure, heart rate, blood glucose and body weight were monitoredthroughout the study. The right middle cerebral artery was transiently occluded (MCAo) for either 20or 30min2 and cerebral blood flow (CBF) was monitored during, 5min prior and 10min after MCAo.After 24h reperfusion mice were culled and brains were collected. After 28 weeks of diet, micereceiving HFD had significantly higher body weight at the time of stroke compared to the controls(45�2g vs 33�3g respectively). Blood pressure, blood glucose and heart rate were not significantlydifferent between study groups prior to induction of ischemic stroke. After 20min MCAo there wasno significant difference in the extent of ischemic infarct in HFD study group compared to controlmice (28�7 mm3 vs 21�11 mm3, p = 0.57 respectively). However after 30min MCAo a significantincrease in infarct volume was observed in HFD animals compared to the controls (53�8 and 23�6respectively, p = 0.01) but no haemorrhagic transformation was detected in any study groups. Theincrease in infarct volume was mainly due to a significant increase in infarct in the cortex andhippocampus in HFD animals compared to the controls (29�4 mm3 vs 8�4 mm3 respectively, p <0.01 and 6.6mm3 vs 0.1mm3 respectively, p = 0.02). Hence, diet-induced obesity worsens strokeoutcome, but this effect is dependent on the length/severity of the ischaemic insult. This detrimentaleffect of diet-induced obesity on stroke outcome was not due to a change in blood pressure, heartrate and/or blood glucose. Further investigations are in progress to evaluate the impact of HFD onimmune profile and peripheral organs prior and after ischemic stroke.This study is funded by Wellcome Trust Fund.