High-intensity interval training (HIIT) is increasingly recommended to individuals with obesity, regardless of empirical evidence. The increased inflammation associated with obesity is well-known. The type of HIIT that is effective in reducing inflammation is yet to be fully elucidated. This study was a randomized trial in which 30 young females with overweight and obesity were randomly allocated to two groups. The study aimed to compare the chronic immunoregulatory impacts of aerobic HIIT (HIIT/AE) and including resistance exercise in HIIT (HIIT/RE) on TLR4 cascades. Both groups engaged in 10 weeks of exercise training, with each session lasting 28 minutes (4 x 4 min). During each interval, the HIIT/AE performed four minutes of all-extremity cycling, whereas the HIIT/RE completed four minutes of combined resistance exercises and all-extremity cycling. The TLR4 pathway gene expression was measured for the TLR4 receptor, downstream adaptors (TIR domain-containing adaptor-inducing interferon-beta (TRIF) and myeloid differentiation factor (MYD) 88), transcriptional factors (nuclear factor kappa B (NF-kappaB), and interferon regulatory factor (IRF) 3), and a negative regulator (tumor necrosis factor (TNF) a-induced protein 3 (TNFAIP3)). The serum levels of TNFalpha, interferon (IFN) gamma, interleukin (IL)-10, and adiponectin were measured. We found that TLR4 (HIIT/RE 0.6 +/- 0.43 versus HIIT/AE 1.24 +/- 0.82, p = 0.02), TRIF (HIIT/RE 0.51 +/- 0.4 versus HIIT/AE 3.56 +/- 0.52, p = 0.001), and IRF3 (HIIT/RE 0.49 +/- 0.42 versus HIIT/AE 0.6 +/- 0.89; p = 0.04) levels were significantly downregulated in HIIT/RE compared to the HIIT/AE, with a significant reduction in serum levels of TNFalpha (pg/ml) (HIIT/RE 22.5 +/- 11.3 to 6.3 +/- 5.3 versus HIIT/AE 19.16 +/- 20.8 to 13.48 +/- 21.7, p = 0.04) and IFNgamma (pg/ml) (HIIT/RE 43.5 +/- 20.6 to 37.5 +/- 4.3 versus HIIT/AE 37.6 +/- 5.6 to 68.1 +/- 22.5, p = 0.03). Adiponectin (ng/ml) (HIIT/RE 8.5 +/- 1.6 to 9.01 +/- 0.8 versus HIIT/AE 8.4 +/- 1.1 to 8.9 +/- 0.6, p > 0.05) and IL-10 (ng/ml) (HIIT/RE 1.4 +/- 0.49 to 1.55 +/- 0.3 versus HIIT/AE 1.9 +/- 1.5 to 1.5 +/- 0.2, p > 0.05) levels did not significantly differ between the two groups. Thus, resistance exercise training augments the immunomodulatory adaptations to HIIT and should be prescribed to people at risk of cardiometabolic disease.

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