Investigating the Effect of Two Types of Aerobic Exercise on <i>SIRT1</i> and <i>AMPK</i> 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. SIRT1 and AMPK pathways help reduce liver fat. This study compared the effects of HIIT and MICT on SIRT1 and AMPK gene expression in mice with diet-induced NAFLD. Methods: In this experimental study, 36 male C57BL/6J mice were randomly divided into NFFD, NFDHIIT, NFDMICT, HFD, HFDHIIT, and HFDMICT groups (n=6 per group). Mice in the NFDHIIT, NFDMICT, HFDHIIT, and HFDMICT groups underwent 8 weeks of treadmill training after 12 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 (0.386±0.012) and SIRT1 (0.647±0.010) genes compared to the NFFD group (AMPK: 0.942±0.013; SIRT1: 1.020±0.063; P&lt;0.001). In mice fed with HFD, both HIIT (AMPK: 0.983±0.039; SIRT1: 1.361±0.072) and MICT (AMPK: 0.865±0.010; SIRT1: 1.214±0.015) significantly increased gene expression compared to the HFD control group (P&lt;0.001). Although HIIT showed a higher increase in AMPK expression than MICT within the HFD groups, this difference was not statistically significant (P=0.219). Similarly, under normal diet conditions, both HIIT and MICT could significantly increase SIRT1 expression compared to the NFFD group (P&lt;0.001 and P=0.019, respectively. However, no significant difference was observed between the two exercise groups in this diet condition (P=0.135). Conclusion: These findings suggest that aerobic exercise, particularly HIIT, may help reduce NAFLD progression through SIRT1/AMPK pathway activation.