INTRODUCTION:
Following physical exercise, fibronectin type III domain-containing protein 5 (FNDC5) is cleaved at the cell membrane to produce irisin, a myokine involved in endothelial function, bone remodeling and integrity, muscle adaptation, and neuroplasticity through the upregulation of brain-derived neurotrophic factor (BDNF). Irisin release is primarily associated with concentric exercise, typically characterized by limited muscle damage. In contrast, eccentric exercise (EE) induces micro-injuries in muscle fibers while eliciting muscle adaptations at a lower metabolic cost. Whether EE promotes neuroplastic effects through systemic irisin release remains unclear. This study investigated the FNDC5/irisin response to EE and its relationship with muscle regeneration and hippocampal BDNF modulation.
METHODS:
Sixteen male rats were randomly assigned to sedentary control (n=8) or EE-trained (n=8) groups. The EE group performed treadmill running for seven consecutive days (30 min/day, 70% maximal aerobic speed) on a −28.7% incline. Animals were euthanized 24h after the final session. The gastrocnemius muscle and the hippocampus were collected for Western blotting and immunofluorescence analyses. Blood samples were obtained immediately post-exercise to evaluate irisin levels.
RESULTS:
EE induced a significant increase in hippocampal BDNF expression. In addition, FNDC5/irisin expression was elevated in gastrocnemius muscle, predominantly in type IIa and IIb fibers, with no significant change in type IIx fibers. Despite enhanced muscle FNDC5 expression, circulating irisin levels remained unchanged. Markers of muscle regeneration (PAX7, MyoD1) were significantly increased following EE. Immunofluorescence analyses revealed an increased number of PAX7- and MyoD-positive cells co-expressing FNDC5.
CONCLUSION:
In summary, EE represents a valuable exercise modality for inducing neuroplastic effects independently of detectable systemic irisin release. The absence of increased circulating irisin despite elevated muscle FNDC5 expression suggests a predominantly autocrine effect that facilitates muscle regeneration following EE.