There is a close and effective interaction between health status and insulin resistance (IR), due to the High-fructose corn syrup - 55% (HFCS-55) used in daily prepared foods and soft drinks. IR clusters are related to an imbalance in pro-and anti-inflammatory adipokines such as secreted frizzled-related protein 5 (SFRP5) and wingless-type mammary tumor virus integration site family, member 5A(WNT5A). WNT5A induces an inflammatory state to induce insulin resistance and further pathologic consequences. Regarding the noninvasive and anti-inflammatory effects of exercise training and vanadium-zinc supplementation, we aimed to investigate the effects of moderate-intensity continuous training (MICT) with vanadium-zinc supplementation on the modulation of insulin resistance induced by high-fructose corn syrup (HFCS) through Wnt-Sfrp5 signaling pathway. METHODS: 40 male Wistar rats (aged 4-6 weeks, 100-150 g) were randomly categorized into 5 groups (n = 8/groups), including (NC) Normal Control, (FC) Fructose Control, and (FCT) Fructose Continuous Training, (FS) Fructose Supplement and (FSCT) Fructose Supplement Continuous Training. The training groups implemented the MICT for 8 weeks followed by the 8 weeks of the HFCS-55 (diluted by tap water to 20%) administration as ad-libitum syrup from the beginning. MICT protocol was 12 minutes of running in the first week increasing to 52 minutes in the last week (speed ~ 20 m/min and slope ~ 15°). About 48 hours after the final training session, serum samples were taken to measure the levels of Insulin, Glucose, GPX (Glutathione Peroxidase), TOC (Total Oxidant Capacity), TAC (Total Anti-Oxidant Capacity), MDA (Malondialdehyde), SOD (Superoxide dismutase) WNT5A, and SFRP5 by chemiluminescence technique. Data were analyzed by dependent sample T-test and one-way ANOVA (P <0.05). RESULTS: Regarding the results of one-way ANOVA, the main effect of 8 weeks of MICT significantly decreased the serum levels of insulin resistance (glucose an
