Long-term intermittent fasting induces sex-dependent changes in small intestine from SAMP8 aged mice

Abstract

Background: Intermittent fasting (IF) is a popular and effective method to decrease body weight. Yet, the effects of IF on aged intestine is unknown. SAMP8 (Senescence Accelerated Mouse-Prone 8) mice are used as a model for studying aging. This study aimed to examine the potential for IF to ameliorate age-associated disturbances in murine jejunum. Methods: Two-month-old male and female SAMP8 mice were randomly assigned to either an IF protocol or an ad-libitum diet (AL) for the 8-month study (n=7-10 group). Fasted mice followed a 24-hour alternate day fasting protocol. At the end of the study mice were euthanized and jejunum stored at −80°C until use for western blot or other assay, and a segment was fixed for histology. Results: IF resulted in significantly less weight gain in both males (22% less, n=7-10, p<0.05) and females (33% less, n=7-8, p<0.05) and response to glucose load (glucose tolerance testing) was comparable in both sexes: area under curve for AL > IF. Interestingly, IF significantly reduced fasting serum glucose levels in males (30% less, n=6, p<0.05), but IF had no effect on fasting serum glucose in females. In jejunum, we assessed: protein expression, health, and morphology. In females, IF led to a 57% decrease in GLUT2 expression (n=5-6, p<0.05) versus AL. GLUT2 moves glucose/galactose and fructose out of the enterocyte into the blood, suggesting restructuring of monosaccharide transport due to IF. IF had no effect on jejunum GLUT5 or SGLT1 expression. Cleaved Caspase-3 expression was decreased by IF in both sexes versus AL. This reduction was greater in females, suggesting a sex-dependent protective role of IF against apoptosis. Moreover, IF induced a significant increase 1.4-fold (n=5=6, p<0.05) in jejunum superoxide dismutase (SOD) activity in both sexes. Jejunum morphology was significantly changed in females only: IF induced both a decrease in villi length (by 21%, n=4/group, p<0.05) and a decrease in wall thickness (by 7%, n=4/group, p<0.05). Conclusions: In both sexes, IF decreased body weight, yet in females resting glucose levels were unchanged by IF. In females, IF reduced monosaccharide absorption out of intestines, yet improved overall intestinal health, increasing antioxidant levels with SOD. These findings collectively highlight the complex effects of IF on cellular processes and demonstrate significant sex-dependent aged intestinal responses. Unraveling the underlying molecular mechanisms driving these sex-dependent IF-induced effects is currently under evaluation. Midwestern-Arizona Alzheimer’s Consortium Grant, Midwestern University Intramural Grant. 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.