Introduction: There is accumulating evidence on the beneficial effect of exercise intervention in the management of metabolic disorders; however, the molecular mechanism is still unclear. Here, the current study aimed to compare the effect of high-intensity interval training (HIIT) and continuous endurance training (CET) on serum and adipose-tissue markers of M1/M2 macrophage polarization. Methods: A total of 45 healthy male Wistar rats were divided into groups of normal chow (n=10) and high-fat diet (HFD) (n=35). Then, rats receiving the HFD were randomly divided into four groups. Training programs were performed for 5 days/week over 10 weeks. The CET protocol included 30 minutes running at 50%-60% of VO 2max . The HIIT protocol consisted of five repeated intervals of 2-minute sprints on the treadmill at 80%-90% VO 2max workload with 1 minute's 30%-35% VO 2max interval for each rat. Then, biochemical parameters were assessed. Macrophage-polarization markers were assessed at mRNA and protein levels by real-time PCR and Western blotting, respectively. Results: Both exercise-training programs, especially HIIT, reversed increased serum biochemical parameters (glucose, triglycerides, cholesterol, Homeostatic Model Assessment of Insulin Resistance, and hsCRP), M1-polarization markers (circulating IL6, TNFα, and adipose-tissue mRNA expression of IL6, TNFα and iNOS), M2 markers (CD206, CD163, and IL10 expression), as well as pIκKB, pNFκB, and NICD expression in HFD-induced diabetes. Conclusion: Our findings suggest that despite devoting less time, the HIIT workout is a more effective intervention for diabetes management. Moreover, HIIT reverses HFD-induced macrophage polarization by targeting the NFκB and NOTCH signaling pathways.
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