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

Abstract 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-o...

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Main Authors: Keshari H. Sudasinghe, Zachary J. White, Stephanie E. Hall
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-09692-7
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author Keshari H. Sudasinghe
Zachary J. White
Stephanie E. Hall
author_facet Keshari H. Sudasinghe
Zachary J. White
Stephanie E. Hall
author_sort Keshari H. Sudasinghe
collection DOAJ
description Abstract 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.
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spelling doaj-art-8d3521c0a3ef43c0923a43b1a95520162025-08-20T04:01:49ZengNature PortfolioScientific Reports2045-23222025-07-0115111010.1038/s41598-025-09692-7Sexual dimorphism in response to intermittent fasting and its impact on the brainKeshari H. Sudasinghe0Zachary J. White1Stephanie E. Hall2Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State UniversityDepartment of Anatomy and Physiology, College of Veterinary Medicine, Kansas State UniversityDepartment of Anatomy and Physiology, College of Veterinary Medicine, Kansas State UniversityAbstract 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.https://doi.org/10.1038/s41598-025-09692-7Intermittent fastingMemorymTOR pathwaySex difference
spellingShingle Keshari H. Sudasinghe
Zachary J. White
Stephanie E. Hall
Sexual dimorphism in response to intermittent fasting and its impact on the brain
Scientific Reports
Intermittent fasting
Memory
mTOR pathway
Sex difference
title Sexual dimorphism in response to intermittent fasting and its impact on the brain
title_full Sexual dimorphism in response to intermittent fasting and its impact on the brain
title_fullStr Sexual dimorphism in response to intermittent fasting and its impact on the brain
title_full_unstemmed Sexual dimorphism in response to intermittent fasting and its impact on the brain
title_short Sexual dimorphism in response to intermittent fasting and its impact on the brain
title_sort sexual dimorphism in response to intermittent fasting and its impact on the brain
topic Intermittent fasting
Memory
mTOR pathway
Sex difference
url https://doi.org/10.1038/s41598-025-09692-7
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