Combined All-Extremity High-Intensity Interval Training Regulates Immunometabolic Responses through Toll-Like Receptor 4 Adaptors and A20 Downregulation in Obese Young Females

Abstract

Metainflammation and malfunctions of toll-like receptor 4 (TLR4) are related to obesity-induced immunometabolic morbidities. There are almost no studies relating exercise training to the TLR4 pathway and its adaptors and negative regulators. Thirty young women with obesity (exercise group and control group) were included in a 10-week all-extremity combined high-intensity interval training program. The immunomodulatory impacts of exercise onTLR4, its related adaptors (TIR domain-containing adaptor-inducing IFN-betaTRIF, myeloid differentiation factor 88 MyD88,and tumor receptor-associated factor 6 TRAF6), transcriptional factors (nuclear factor NF-kappa Band interferon regulatory factor 3 IRF3), and negative regulator (A20) mRNA levels were assessed by real-time PCR. Also, the serum concentration of TLR4 final products (tumor necrosis factor alpha TNF alpha and interferon gamma IFN gamma) was measured by ELISA. Cardiorespiratory and body composition parameters were tested, as well. There was a significant improvement in body composition and cardiorespiratory fitness. This intervention downregulated TLR4 (from 2.25 +/- 1.07 to 0.84 +/- 1.01), MyD88 (from 4.53 +/- 5.15 to 1.27 +/- 0.88), NF-kappa B (from 1.61 +/- 2.03 to 0.23 +/- 0.39), IRF3 (from 1.22 +/- 0.77 to 0.25 +/- 0.36), and A20 (from 0.88 +/- 0.59 to 0.22 +/- 0.33) levels and reduced the TNF alpha concentrations (from 22.39 +/- 11.43 to 6.26 +/- 5.31) significantly in the exercise group, while no statistically significant change was found inTRIFandTRAF6expression and IFN gamma circulating levels. It is concluded that long-term exercise modifies the inflammatory pathways and modulates the immune function at the early stages of inflammation initiation in circulating immune cells. Accordingly, we suggest time-efficient exercise protocols as a possible therapy approach for the prevention of M1 polarization.