Acute high-fat feeding leads to disruptions in glucose homeostasis and worsens stroke outcome.

Chronic consumption of diets high in fat leads to obesity and can negatively affect brain function. Rodents made obese by long-term maintenance on a high-fat diet have worse outcome after experimental stroke. High-fat consumption for only three days does not induce obesity but has rapid effects on the brain including memory impairment. However, the effect of brief periods of high-fat feeding or high-fat consumption in the absence of obesity on stroke is unknown. We therefore tested the effect of an acute period of high-fat feeding (three days) in C57B/6 mice on outcome after middle cerebral artery occlusion (MCAo). In contrast to a chronic high-fat diet (7.5 months), an acute high-fat diet had no effect on body weight, adipose tissue, lipid profile or inflammatory markers (in periphery and the brain). Three days of high-fat feeding impaired glucose tolerance, increased plasma glucose and insulin and brain expression of the glucose transporter GLUT-1. Ischaemic damage was increased (48%) in mice fed an acute high-fat diet, and was associated with a further reduction in GLUT-1 in the ischaemic hemisphere. These data demonstrate that only a brief period of high-fat consumption has a negative effect on glucose homeostasis and worsens outcome after ischaemic stroke.