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Acute Modulation of Circulating Exerkines Responses to a Circuit and Traditional Resistance Training in Young Adults

Submitted:

03 April 2026

Posted:

07 April 2026

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Abstract
Evidence suggests that physical activity promotes bone health through mechanical loading and biochemical signaling between bone and muscle tissues. A class of signaling molecules known as exerkines is a key mediator of bone–muscle crosstalk. Although exercise regulates osteokines, the acute exerkine responses across different exercise modalities remain unclear. This randomized repeated-measures crossover study compared acute changes in serum sclerostin (SCL), dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteopontin (OPN), brain-derived neurotrophic factor (BDNF), irisin, and interleukin 6 (IL-6) following circuit training (CT) (cycle ergometer, push-up, step-ups, medicine ball twist, and front squats with kettlebell for three sets) and traditional resistance (TR) exercise (3 sets 10 repetitions 80% 1RM for leg press, seated cable row, barbell bench press, dumbbell deadlifts, and dumbbell seated shoulder press) in healthy young adults (n=12). Participants performed two protocols separated by 2-week wash-out periods. Blood samples were analyzed before exercise training (pre), immediately post-exercise (IP), and 30 minutes post-exercise (30P) for all exerkines using ELISA. There was a significant interaction between protocol, timepoint, and sex (p=0.038) for SCL levels. There was a significant interaction between protocol, timepoint, and sex for SCL levels (p < 0.05). In males, SCL levels increased from Pre to IP under both training protocols (CT: 0.10 ± 0.02 ng/mL to 0.14 ± 0.02 ng/mL; TR: 0.20 ± 0.02 ng/mL to 0.21 ± 0.02 ng/mL). In both protocols, SCL levels decreased from IP to 30 P (CT: 0.14 ± 0.02 to 0.10 ± 0.01 ng/ml; TR: 0.22 ± 0.02 to 0.17 ± 0.02 ng/ml). In females, SCL levels increased from Pre to IP under both training protocols (CT: 0.03 ± 0.02 ng/mL to 0.06 ± 0.02 ng/mL; TR: 0.07 ± 0.02 ng/mL to 0.13 ± 0.02 ng/mL). There was a significant time effect for OPN and RANKL concentrations. Marginal means for the time point showed that OPN was significantly higher at the Pre time point. Post hoc analyses showed that OPN levels significantly decreased from 30P to Pre (18.84 ± 0.92 to 15.69 ± 1.32 pg/mL) (p=0.08). Similarly, RANKL showed a significant increase from Pre (0.38 ± 0.04 pg/mL) to 30P (0.57 ± 0.06 pg/mL) (p=0.02); otherwise, there were no significant differences between protocols or sexes. Irisin significantly decreased from Pre (28761.73 ± 238.52 pg/mL) to IP (2364.85 ± 243.79 pg/mL) in both protocols (p=0.01). DKK-1, BDNF, and IL-6 levels were only different between protocols (p< 0.01). SCL and BDNF levels were expressed higher in the TR protocol, whereas DKK-1, IL-6, and Irisin levels were expressed higher in the CT protocol. Overall, the findings suggest that SCL, RANKL, OPN, and irisin responded to the exercise bout, while the exerkines did not show meaningful changes over time.
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Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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