SESN2 mediates resistance training-induced improvements in exercise performance and energy metabolism in C57BL/6J mice.

Long-term resistance training promotes skeletal muscle hypertrophy and boosts energy metabolism. The stress-inducible protein, SESN2 is a mediator of aerobic training benefits. However, whether SESN2 mediates resistance training to promote skeletal muscle hypertrophy and energy metabolism remains elusive. In this study, eight-week-old C57BL/6J male wild-type (WT) and SESN2-/- mice were subjected to resistance training intervention for 12 weeks. Our results revealed that SESN2 deficiency weakened the effects of resistance training on the increase of grip strength, maximum load capacity, time to exhaustion, and grid suspension time. SESN2 promoted skeletal muscle hypertrophy by inhibiting protein degradation in response to resistance training. Moreover, SESN2 ablation blocked the resistance training-induced improvements in oxygen consumption, carbon dioxide production and energy expenditure. Glycolysis and tricarboxylic acid cycle in skeletal muscle of SESN2-/- mice remain unchanged after resistance training. Furthermore, SESN2 deletion did not alter the expression of key metabolic enzymes in glycolysis and tricarboxylic acid cycle in both atrophied skeletal muscle and resistance exercise preconditioned muscle. These results imply that the SESN2 is a crucial regulator in facilitating the beneficial effects of resistance training on exercise performance, skeletal muscle mass and energy metabolism. This study contributes to the understanding of the mechanisms by which resistance training promotes skeletal muscle energy metabolism.