Sinha_2026_Diabetes__

This study aimed to identify novel exercise-induced myokines and their role in improving insulin sensitivity and reducing inflammation. We identified neuroligin-3 (NLGN3) as an exercise-induced mediator that enhances insulin sensitivity and alleviates inflammation. Exercise-induced NLGN3 upregulation or recombinant NLGN3 administration improved metabolic function in high-fat diet-fed mice via neurexin-1 and -3 (NRXN1/3), but these benefits were lost upon NRXN1/3 ablation. NLGN3 emerges as a key mediator of exercise-driven metabolic benefits and a promising therapeutic target for obesity-associated insulin resistance.