High-Intensity Interval Training Reversed High-Fat Diet–Induced M1-Macrophage Polarization in Rat Adipose Tissue via Inhibition of NOTCH Signaling

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.