Abstract

Objectives: Intermittent Fasting (IF), time-restrictive food intake, has been shown to improve cognitive functions and reduce age-related behavioral impairments in rodent models. Our prior studies have found that IF intervention has significantly reduced body weights and food intake in male Fsher-344 rats; however, females did not display IF-induced declines in body weights and food intake. The exact mechanism for the sex differences in body weight and food intake during IF is not fully understood. Factors such as shifts in body composition and metabolic demand may contribute to variations in body weight shifts and food consumption. We hypothesized that changes in body composition and metabolic shifts may contribute to sex differences in body weight and food consumption in response to IF. Methods: Thirty-six, two-month-old male and female Fisher-344 rats were randomly assigned to four groups: ad libitum (AL) male, IF males, AL females, IF females. The AL group had 24/7 access to food and water while the IF group had 24/7 access to water and full access to food on an every-other-day basis for four weeks. After four weeks of IF intervention, rats were introduced to a metabolic rate (respiratory gas analyzer) and a grip strength test. In addition, body scans were performed using a Lunar Piximus rodent densitometer, (GE Lunar corporation). Group differences were analyzed with two-way ANOVA per Prism Graph Pad software. Following body scans, animals were euthanized, and tissues were sectioned, weighted, and stored for future analysis (brain, skeletal muscles, and adipose tissues). Results: IF intervention resulted in reduced body mass in males (vs. AL males, p<0.0001) but not in females. Average daily food intake tended to be lowered in IF groups compared to their AL counterparts. Densitometry results revealed that the IF males had a decreased lean mass (vs. AL males, p<0.0001) and fat mass (vs. AL males, p<0.0001). Neither lean mass nor fat mass were changed in females as a result of IF. After two weeks of IF, O2 consumption was lowered in IF females compared to AL (P=0.0215 fed-state, P=0.0030 fast-state); however, no significant effect was seen in males. Grip strength was not significant among groups. Conclusions: In the present study, IF males significantly reduced body weights, as well as both fat and lean mass while females did not exhibit IF-induced changes. Interestingly, IF females displayed declines in oxygen consumption while males did not change. The decrease in oxygen consumption (slower metabolism) in IF females can be seen as a compensatory mechanism by the body to conserve energy and maintain body weights and composition shifts. The sexual dimorphic effect of body composition shifts is intriguing and the metabolic adaptations in skeletal muscle/fat tissues will be the focus of follow-up investigations. Funding source: P20GM113109 Cognitive and Neurobiological Approaches to Plasticity (CNAP) center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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