Obesity is commonly associated with immunometabolic dysfunctions. Activation of inflammatory macrophages through TLR4 (toll-like receptor 4) and the anti-inflammatory impact of exercise have been and are the new concerns among researchers. A new short-term combined high-intensity interval training was proposed in young sedentary overweight/obese females. All participants were allocated to one of two groups: the exercise group (EG) and the control group (CG), where the EG participated in a 2-week combined training and the CG continued its routine lifestyle. Gene expression levels of TLR4, NF-κB(nuclear factor κB), and IRF3 (interferon regulatory factor 3) were assessed by real-time PCR. Physiological, anthropometric, and biomedical metabolic factors were assessed. The between-group comparisons indicated a tendency to a decrease in NF-κB gene expression in the EG. The IRF3 levels were not significantly changed compared to CG and the levels before training. Fasting glucose levels and β-cell function revealed a significant improvement in EG. These findings indicated that this protocol decreased meta-inflammation levels and improved insulin resistance independent of body composition changes. Consequently, combined training may be recommended as a therapeutic approach in metabolic diseases.

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