Impact of High-fat Diet Exposure on Metabolism, Cerebral Circulation and Cognition in Juvenile and Adolescent LDL-receptor Knockout Mice

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Obesity is a serious and global health threat. Similar to adult obesity, early life obesity is on the rise and associated to various health conditions and cognitive impairment. Multiple lines of evidence suggest biological mechanisms and critical developmental periods in early life, important periods of brain maturation, on which obesity can have detrimental effects. Here, the impact of a high-fat diet (HFD) on metabolism, cerebral circulation and cognition are investigated in a genetic low-density-lipoprotein receptor knockout (LDLr-/-) mouse model of obesity. HFD was initiated in male and female mice at juvenile – 6 weeks – or adolescent age – 12 weeks – and was maintained for 18 and 12 weeks respectively, in an attempt to identify a sensitive period in both genders where HFD effects are particularly harmful. Juvenile and adolescent HFD resulted in weight gain in males, while juvenile HFD caused only a slight weight increase in females. In males, a juvenile HFD seems to decrease energy expenditure, as seen in open field test behavior. HFD exposure did not affect plasma glucose, cerebral blood flow or hippocampus-dependent learning and memory capabilities during the Morris water maze in either gender. Because sample sizes were small, limited evidence indicates that primarily juvenile HFD exposure has obesogenic effects in the LDLr-/- model, but a juvenile or adolescent HFD does not alter cerebral circulation or cognitive functioning in young male and female LDLr-/- mice.
Faculteit der Sociale Wetenschappen