Objective: Type 2 diabetes, as one of the most common metabolic disorders, is associated with insulin resistance and impaired glucose homeostasis. Through the induction of oxidative stress and chronic inflammation, it leads to progressive damage in liver tissue. This study aimed to investigate the effects of eight weeks of high-intensity interval training (HIIT) and curcumin supplementation, separately and in combination, on the expression of key inflammatory genes including RELMα, VCAM-1, and CXCL1 in the liver tissue of male diabetic rats.

Methodology: In this quasi-experimental study, 50 male Wistar rats were randomly divided into five groups of ten each: healthy control, diabetic control, diabetes + curcumin, diabetes + HIIT, and diabetes + HIIT + curcumin. Type 2 diabetes was induced first by eight weeks of feeding with a high-fat diet (60% of calories from fat), followed by a single intraperitoneal injection of streptozotocin (STZ) at a dose of 30 mg/kg. The HIIT training protocol was performed for eight weeks, five sessions per week, consisting of four-minute running bouts at 80-90% of maximal oxygen consumption (VO₂max) alternating with three-minute active recovery periods. Curcumin supplement (95% purity) was administered daily at a dose of 100 mg/kg body weight by oral gavage. After the interventions, the expression of target genes in liver tissue was measured using Real-time PCR and the 2^-ΔΔCT method relative to the GAPDH reference gene. Data analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test, with a significance level set at p < 0.05.

Results: The results showed that the expression of all three genes, RELMα, VCAM-1, and CXCL1, was significantly increased in the diabetic control group compared to the healthy control group (p < 0.05). HIIT alone significantly reduced RELMα expression compared to the diabetic control group (p < 0.05) but had no significant effect on the expression of VCAM-1 and CXCL1 (p > 0.05). Curcumin alone also significantly reduced RELMα expression (p < 0.001) but did not show a significant effect on the other two genes (p > 0.05). In contrast, the group receiving the combination of HIIT and curcumin showed a significant reduction in the expression of all three genes, RELMα, VCAM-1, and CXCL1, compared to the diabetic control group, indicating a synergistic effect of these two interventions (p < 0.05).

Conclusion: The findings of this study indicate that the combination of high-intensity interval training and curcumin supplementation is more effective than either intervention alone in reducing the expression of key inflammatory genes in the liver of diabetic rats. Therefore, this combined approach can be considered as an effective non-pharmacological and complementary strategy for liver protection and management of inflammatory complications resulting from type 2 diabetes.