Effect of High-Intensity Interval Training and Fisetin on the Gene Expression of NLRP3 and IL18 in Kidney Tissue of Mice with Type 2 Diabetes

Introduction: Obesity is closely associated with type 2 diabetes, inflammation and kidney dysfunction. In this study, the effect of high-intensity interval training (HIIT) and Fisetin on NLRP3 and IL18 gene expression in kidney tissue of mice with type 2 diabetes was investigated. Methods: In this experimental study, 30 male C57bl/6 mice were randomly divided into 2 main control groups (6 mice) and a high-fat diet (24 mice). T2D was induced by a high-fat diet over 16-week period. Upon confirming T2D, diabetic mice were randomly allocated into diabetes, diabetes-exercise, diabetes-Fisetin, and diabetes-exercise-Fisetin groups. The Fisetin supplement was injected via intraperitoneal injection at a dosage of 20 mg/kg/day. The HIIT protocol consisted of 2-minute intervals at an intensity of 80-110% of maximal aerobic power (VO2max) followed by 2-minute rest periods at an intensity of 50% of VO2max, with 2-8 repetitions over 8 weeks. NLRP3 and IL-18 gene expression in kidney tissue was determined. Data analysis utilized one-way analysis of variance along with SPSS Software version 16 (p<0.05). Results: Following 8 weeks, NLRP3 (p<0.001) and IL-18 (p<0.001) gene expression increased in the diabetic group compared to the control group (p<0.001). Additionally, gene expression of NLRP3 and IL-18 was significantly lower in the HIIT, fisetin, and combined intervention groups when compared to the diabetes group (p<0.001). The effect of the combined intervention in reducing gene expression of these variables was significantly higher compared to the other two interventions (p<0.0001). Conclusion: HIIT, Fisetin and their combined intervention can protect diabetic kidney tissue by decreasing inflammation via inhibition of the NLRP3/IL-18 axis gene expression pathway.