Research Progress on Exercise Preventing and Treating Depression Through Regulation of Irisin postprint

Abstract: The pharmacological treatment of depressive disorder is often limited by slow onset of action and significant side effects, highlighting the importance of exploring safe and effective non-pharmacological intervention strategies. Exercise therapy, as a simple and low-cost intervention, has been shown to significantly alleviate depressive symptoms; however, its underlying biological mechanisms require systematic elucidation. This study presents a systematic review focusing on irisin, a novel myokine. It finds that regular exercise activates the PGC-1α/FNDC5 pathway in skeletal muscle, promoting irisin secretion. After crossing the blood-brain barrier, irisin alleviates depressive symptoms by forming a "muscle-brain" multi-target intervention loop through inhibiting neuroinflammation, upregulating brain-derived neurotrophic factor expression, enhancing neuroplasticity, and modulating the gut-brain axis. The regulatory effects on irisin vary across different exercise modalities, with moderate-intensity aerobic exercise and high-intensity interval training showing more pronounced effects. In summary, this study identifies the irisin-mediated muscle-brain axis as one of the core mechanisms underlying the antidepressant effects of exercise, offering a new research perspective for the prevention and treatment of depressive disorder, and demonstrating promising potential for clinical and public health translation.