Sexual dimorphism in response to intermittent fasting and its impact on the brain

Intermittent fasting (IF) has been shown to improve cognitive functions in rodent models. In addition, IF significantly reduces mammalian target of rapamycin (mTOR) expression. We hypothesized that IF would reduce mTOR signaling while improving memory and strength in healthy rats. 10-week-old male and female Fischer-344 rats (n = 48) were randomly assigned to four groups: ad libitum (AL)-male, IF-male, AL-female, IF-female. The IF group had full access to food on an every-other-day basis for 10 weeks. After 10 weeks, memory and strength were assessed. Following testing, brain and skeletal muscles were isolated, weighed and mTOR pathway proteins were quantified via Jess Simple Western. Prism GraphPad was used to determine group differences (one-way ANOVA) and correlations (Pearson) with alpha 0.05. After 10 weeks of IF, only males experienced IF-induced body mass (p < 0.0001) and average daily food intake (p = 0.014) declines. Further, IF males displayed better memory performance compared to AL counterparts (p = 0.0186). Brain mass was lower in both males (p = 0.0038) and females (p = 0.0205) compared to respective AL counterparts while hippocampal mass was maintained. Weight loss in males correlated with reduced mTOR expression in the brain cortex (r = 0.546, p = 0.006) and mTOR was significantly reduced in IF males cortex (vs. AL males p = 0.0003) and skeletal muscle (EDL: vs. AL males p = 0.0377). IF reduced average food intake and inhibited the mTOR pathway in the cortex of male rats while improving memory. IF did not have a significant effect in female rats.