The Effect of High-Intensity Interval Training and Rutin Supplementation on the Expression of PGC-1α, SIRT1, and TFAM Genes in the Cardiac Tissue of Male Rats with Type 2 Diabetes

Abstract

Background and Objective: Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by chronic hyperglycemia, insulin resistance, and impaired cellular energy homeostasis. One of the major complications of T2DM is its detrimental effect on the cardiovascular system, where prolonged metabolic stress leads to structural and functional alterations in cardiac tissue. Mitochondria, as the primary organelles responsible for cellular energy supply, play a crucial role in maintaining normal myocardial contractility and function. Among the key regulators of mitochondrial health are PGC-1α, SIRT1, and TFAM, which are strongly implicated in mitochondrial biogenesis and metabolic adaptation. Evidence indicates that diabetes downregulates the expression of these genes, thereby disrupting mitochondrial biogenesis. This impairment in mitochondrial biogenesis reduces cardiac energy availability, promotes contractile dysfunction, and ultimately contributes to the development of diabetic cardiomyopathy and heart failure.Consequently, non-pharmacological interventions such as structured exercise and natural compounds have gained attention as potential therapeutic strategies. High-intensity interval training (HIIT), owing to its intense and intermittent nature, has been shown to stimulate mitochondrial biogenesis and improve energy metabolism. Similarly, rutin, a natural flavonoid with potent antioxidant and anti-inflammatory properties, has been reported to protect cardiomyocytes against oxidative stress and may also influence mitochondrial biogenesis pathways. Therefore, the present study aimed to investigate the independent and combined effects of HIIT and rutin supplementation on the expression of PGC1-α, SIRT1, and TFAM in the cardiac tissue of type 2 diabetic rats
Materials and Methods: In this experimental study, 40 male Wistar rats with type 2 diabetes (induced by a single intraperitoneal injection of streptozotocin) were selected and randomly divided into five groups of eight: (1) diabetic control (DC), (2) normal control (NC), (3) high-intensity interval training (D+HIIT), (4) rutin supplementation, and (5) high-intensity interval training with rutin supplementation (D+HIIT+R).The HIIT groups trained for 4 weeks, 5 sessions per week (each session consisting of 5–6 intervals of 2 minutes at 80–90% of maximal running speed, interspersed with 1-minute recovery at 30% of maximal speed) on a rodent treadmill. Rutin-receiving groups were administered rutin orally via gavage at a dose of 100 mg/kg/day for 4 weeks. Data were analyzed using one-way ANOVA, and Tukey's post hoc test (p<0.05).
Results: Induction of diabetes significantly reduced the expression of PGC1-α, SIRT1, and TFAM genes in the diabetic control (DC) group compared to the normal control (NC) group (p<0.05). Each of the interventions, high-intensity interval training and rutin supplementation alone, significantly increased the expression of these genes (PGC1-α: p=0.001; SIRT1: p=0.001; TFAM: p=0.001). Moreover, the combination of high-intensity interval training and rutin supplementation showed a significant effect in increasing the expression of PGC1-α (p=0.001), SIRT1 (p=0.001), and TFAM (p=0.001).
Conclusion: It seems that high-intensity interval training and rutin supplementation, either individually or in combination, can improve the expression of PGC1-α, SIRT1, and TFAM genes in the cardiac tissue of male rats with type 2 diabetes.