Background and Objective: Type 2 diabetes mellitus (T2DM) is one of the most prevalent metabolic disorders worldwide and has become a major public health challenge due to its chronic complications and multifactorial pathophysiology. This disease is associated with impaired liver function and an increased risk of hepatic disorders, imposing a substantial burden on healthcare systems. Therefore, the present study aimed to investigate The effect of the eighth week of high-intensity interval training (HIIT) on some hepatokines (FGF21, ANGPTL6 and HFREP1) in the body tissue of mice infected with type 2.
Materials and Methods In this experimental study, 20 adult male NMRI mice (8 weeks old; 26.0 ± 3.22 g) were randomly assigned to four groups (n = 5 per group): healthy control, healthy training, diabetic control, and diabetic training. Type 2 diabetes was induced through a 5-week high-fat diet (HFD) followed by a single intraperitoneal injection of streptozotocin (STZ). Mice with fasting blood glucose levels above 126 mg/dL were considered diabetic and allocated to the diabetic groups. The training groups performed a high-intensity interval training (HIIT) protocol for 8 weeks, 5 days per week, at 60–90% of maximal running velocity (Vmax), with the number of intervals progressively increasing from 10 in the first week to 13 in the eighth week (2:2 work-to-rest ratio). Forty-eight hours after the final training session, animals were anesthetized, and blood and liver tissue samples were collected under sterile conditions. Hepatic gene expression levels of FGF21, ANGPTL6, and HFREP1 were determined using real-time polymerase chain reaction (RT-PCR). Differences among groups were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test. Statistical analyses were performed using SPSS version 27, with the significance level set at p < 0.05.
Results Induction of type 2 diabetes resulted in a significant upregulation of hepatic ANGPTL6, HFREP1, and FGF21 gene expression in diabetic mice (p = 0.001, p = 0.001, and p = 0.01, respectively). In contrast, eight weeks of HIIT significantly reduced the expression of ANGPTL6 and HFREP1 in diabetic mice (p = 0.001 and p = 0.01, respectively), while further enhancing FGF21 expression compared with diabetic controls (p = 0.001).
Conclusion: The observed modulation of hepatic gene expression likely reflects enhanced metabolic adaptations, attenuation of diabetes-induced hepatic stress, and activation of regulatory pathways involved in energy balance and glucose homeostasis. Collectively, these findings suggest that high-intensity interval training (HIIT) may serve as an effective non-pharmacological intervention for mitigating metabolic and hepatic dysfunction associated with type 2 diabetes, potentially through the regulation of hepatokine-mediated signaling pathways.