Resistance exercise training augments the immunomodulatory adaptations to aerobic high-intensity interval training.

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 × 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-β (TRIF) and myeloid differentiation factor (MYD) 88), transcriptional factors (nuclear factor kappa B (NF-κB), and interferon regulatory factor (IRF) 3), and a negative regulator (tumor necrosis factor (TNF) a-induced protein 3 (TNFAIP3)). The serum levels of TNFα, interferon (IFN) γ, interleukin (IL)-10, and adiponectin were measured. We found that TLR4 (HIIT/RE: 0.6 ± 0.43 vs. HIIT/AE: 1.24 ± 0.82, p = 0.02), TRIF (HIIT/RE: 0.51 ± 0.4 vs. HIIT/AE: 3.56 ± 0.52, p = 0.001), and IRF3 (HIIT/RE: 0.49 ± 0.42 vs. 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 TNFα (pg/ml) (HIIT/RE: 22.5 ± 11.3 to 6.3 ± 5.3 vs. HIIT/AE: 19.16 ± 20.8 to 13.48 ± 21.7, p = 0.04) and IFNγ (pg/ml) (HIIT/RE: 43.5 ± 20.6 to 37.5 ± 4.3 vs. 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 vs. 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 vs. 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.