Sex-Dependent Wheel Running Effects on High Fat Diet Preference, Metabolic Outcomes, and Performance on the Barnes Maze in Rats

Abstract

Excessive and prolonged intake of highly palatable, high fat (HF) foods contributes to the pathogenesis of obesity, metabolic syndrome, and cognitive impairment. Exercise can restore energy homeostasis and suppress HF diet preference in rats. However, it is unclear if exercise confers similar protection against the detrimental outcomes associated with a chronic HF diet preference and feeding in both sexes. We used our wheel running (WR) and two-diet choice (chow vs. HF) paradigm to investigate the efficacy of exercise in reversing HF diet-associated metabolic and cognitive dysregulation in rats, hypothesizing that beneficial effects of exercise would be more pronounced in males. All WR rats showed HF diet avoidance upon running initiation, and males, but not females, had a prolonged reduction in HF diet preference. Moreover, exercise only improved glucose tolerance and insulin profile in males. Compared to sedentary controls, all WR rats improved learning to escape on the Barnes maze. Only WR females increased errors made during subsequent reversal learning trials, indicating a sex-dependent effect of exercise on behavioral flexibility. Taken together, our results suggest that exercise is more effective at attenuating HF-associated metabolic deficits in males, and highlights the importance of developing sex-specific treatment interventions for obesity and cognitive dysfunction.

Ageing, Cognitive Decline, and Effects of Physical Exercise: Complexities, and Considerations from Animal Models

“…A study examining sex differences in voluntary wheel running has shown that female rats voluntarily run on wheels daily for higher distances compared to males [44]. Similarly, more recent studies have reported higher numbers of daily wheel revolutions in female compared to male rats [47,48], indicative of higher voluntary running activity in female compared to male rodents. Interestingly, ovariectomized 3-month-old female Sprague-Dawley rats run shorter daily distances on wheels compared to ovariectomized rats treated with estrogen replacement, suggesting a potential role of the sex hormone estrogen in running distance [49,50].…”

The Aging Human Liver: The Weal and Woe of Evolutionary Legacy

“…In this regard, white adipose tissue (WAT) should be considered as an essential variable in the equation of aging-dependent changes favoring the development of chronic liver disease. Moreover, prolonged detrimental eating habits feeding adipocytes sum up over a lifetime [74] to take their toll in old age. The key task of WAT is to maintain energy homeostasis: Upon excess energy availability, it increases lipid storage and systemically communicates nutritional abundance, while releasing stored triglycerides upon energy depletion as free fatty acids to support catabolism.…”

Morris water maze: a versatile and pertinent tool for assessing spatial learning and memory

“…The BM was first introduced by Carol Barnes in 1979, a few years after the development of the RAM, to study spatial memory in rats [ 64 , 65 ]. To date, it has been primarily applied in small rodents, such as mice [ 65 , 66 , 67 ] and rats [ 68 , 69 , 70 ]. The maze consists of an elevated circular PVC platform (122 cm diameter) supported by an aluminum support frame containing equally spaced holes.…”