Endurance training increases tmTNF-α and IL-6 levels in several vital organs in rats: relationship with hypoxia markers.

BACKGROUND

Although endurance training is known to induce systemic adaptations involving inflammatory and hypoxia-related signaling, tissue-specific protein responses remain incompletely understood. Therefore, this study examined the effects of endurance training on inflammatory cytokines and hypoxia markers across multiple organs.

METHODS

Male Wistar rats performed treadmill running (30-60 min/day, 5 days/week) for 8 weeks. Protein expression of interleukin 6 (IL-6), transmembrane tumor necrosis factor-alpha (tmTNF-α), soluble TNF-α (sTNF-α), hypoxia-inducible factor 1 subunit alpha (HIF-1α), and lysine demethylase 6A (KDM6A) was assessed in the lungs, liver, skeletal muscle, heart, and brain.

RESULTS

Endurance training increased IL-6 protein levels in the lungs, liver, skeletal muscle, and heart, but decreased them in the brain. It also increased tmTNF-α protein levels in the lungs, liver, skeletal muscle, and heart, but decreased them in the brain; it did not affect sTNF-α protein levels in any organ. Hypoxia markers responded to endurance training in an organ-specific manner: HIF-1α and KDM6A protein levels increased in the lungs, liver, and heart, whereas KDM6A protein levels increased while HIF-1α protein levels were unchanged or decreased in the brain and skeletal muscles, respectively.

CONCLUSION

Endurance training induces organ-specific regulation of inflammatory and hypoxia-related proteins. The differential responses of TNF-α isoforms suggest distinct roles of local inflammatory signaling in exercise-induced adaptations. Of particular interest is the observed anti-inflammatory effect of endurance training in the brain, indicating distinct regulatory mechanisms within the CNS.