Investigating the Effect of Two Types of Aerobic Exercise on SIRT۱ and AMPK Gene Expression Regulation in an Animal Model of Non-Alcoholic Fatty Liver Disease

Background and aims: NAFLD, marked by liver fat buildup, lacks approved drug treatments. SIRT۱ and AMPK pathways help reduce liver fat. This study compared the effects of HIIT and MICT on SIRT۱ and AMPK gene expression in mice with diet-induced NAFLD. Methods: In this experimental study, ۳۶ male C۵۷BL/۶J mice were randomly divided into NFFD, NFDHIIT, NFDMICT, HFD, HFDHIIT, and HFDMICT groups (n=۶ per group). Mice in the NFDHIIT, NFDMICT, HFDHIIT, and HFDMICT groups underwent ۸ weeks of treadmill training after ۱۲ weeks of HFD or normal diet feeding. The data were analyzed using two-way ANOVA and Tukey’s post-hoc test. Results: HFD significantly decreased the expression of AMPK (۰.۳۸۶±۰.۰۱۲) and SIRT۱ (۰.۶۴۷±۰.۰۱۰) genes compared to the NFFD group (AMPK: ۰.۹۴۲±۰.۰۱۳; SIRT۱: ۱.۰۲۰±۰.۰۶۳; P<۰.۰۰۱). In mice fed with HFD, both HIIT (AMPK: ۰.۹۸۳±۰.۰۳۹; SIRT۱: ۱.۳۶۱±۰.۰۷۲) and MICT (AMPK: ۰.۸۶۵±۰.۰۱۰; SIRT۱: ۱.۲۱۴±۰.۰۱۵) significantly increased gene expression compared to the HFD control group (P<۰.۰۰۱). Although HIIT showed a higher increase in AMPK expression than MICT within the HFD groups, this difference was not statistically significant (P=۰.۲۱۹). Similarly, under normal diet conditions, both HIIT and MICT could significantly increase SIRT۱ expression compared to the NFFD group (P<۰.۰۰۱ and P=۰.۰۱۹, respectively. However, no significant difference was observed between the two exercise groups in this diet condition (P=۰.۱۳۵). Conclusion: These findings suggest that aerobic exercise, particularly HIIT, may help reduce NAFLD progression through SIRT۱/AMPK pathway activation.