Abstract
BackgroundIncreasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats. MethodsWe examined markers for inflammation and brain plasticity in the hippocampi of LCR rats and compared them to HCR rats. The effect of age was determined by studying the rats at a young age (8 weeks) and later in life (40 weeks). We used western blots and immunohistochemistry to quantify the expression of target proteins. ResultsOur study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pronounced with age. The expression of synaptic proteins was higher in young animals relative to older ones. Brain inflammation tended to be higher in LCR rats than it was in the HCR rats, and more prominent in older rats than in young ones. ConclusionOur study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is also linked with reduced hippocampal structural plasticity at a young age. Our results also suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance.
Highlights
The human population is getting out of shape, as the worldwide number of adults with obesity has reached 2 billion and is constantly increasing (WHO, 2017)
We did not perform a full body composition analysis because previous studies have already shown that the low-capacity runner (LCR) rats have more body fat compared to high-capacity runner (HCR) rats (Stephenson et al, 2012)
Serum glucose concentration was higher in young rats than it was in the old rats in both lines, but again, no differences was seen between the rat lines
Summary
The human population is getting out of shape, as the worldwide number of adults with obesity has reached 2 billion and is constantly increasing (WHO, 2017). We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats. Results: Our study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pro nounced with age. Conclusion: Our study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is linked with reduced hippocampal structural plasticity at a young age. Our results suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance
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