The influence of a high-fat diet on metabolic functioning, cognition, cerebrovasculature and brain structure in juvenile and adolescent LDL receptor knock-out mice

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Behaviour, Preclinical Imaging Centre, Nijmegen, The Netherlands Objective: The prevalence of obesity in children and adolescents is high and associated with metabolic syndrome and cognitive problems. Better understanding of the characteristics and consequences of obesity in children and adolescents is needed for the development of interventions. Therefore, this study focused on examining the effects of an early (childhood) or late (adolescent) intake of a high fat diet (HFD) on metabolic status, cognition and brain function and structure in LDLr -/- mice. Materials and methods: Male and female LDLr-/- mice were divided into three different diet groups, a control group and start of a HFD at 6 weeks and one group at 12 weeks of age. At 24 weeks the mice were investigated in the open field test, Morris water maze, and MRI. Furthermore, faeces, blood pressure and blood samples were collected. Results: The HFD led to increased body weight and weight of fat depots, less motor activity, increased vasoactivity and alterations in white matter and gray matter integrity in the hippocampus, motor cortex and optic tract. However, no effects on systolic blood pressure, learning and memory nor cerebral blood flow were found. Overall, male mice showed a higher body weight and blood glucose values compared to females, whereas no differences were found between early (childhood) or late (adolescent) intake of a HFD. Conclusion: Our results showed only minor diet and gender effects on cognition and brain function and structure in early (childhood) and late (adolescent) age. Some effects of HFD were found on metabolic functioning, and were more prevalent in males compared to females. We suggest that the young age and relative short period of HFD have pr
Faculteit der Sociale Wetenschappen