Sex- and fiber type-specific remodeling of the muscle proteome implicates CSRP3 in resistance training-induced hypertrophy.

Skeletal muscle hypertrophy is a hallmark of resistance training that improves health and longevity. However, despite physiological differences between sexes and fiber types, the underlying proteome changes with resistance training have not been studied in a sex- and fiber type-specific manner. Herein, we show sex- and fiber type-specific remodeling of the human skeletal muscle proteome following 8 weeks of resistance training. Type II fibers exhibited much greater adaptations across both sexes, whereas the main sex difference was a greater remodeling of intermediate filaments in females. Of proteins that were specifically upregulated in type II fibers, overexpression of CSRP3 increased muscle mass in mice, indicating a role of fiber type-specific upregulation of CSRP3 in muscle hypertrophy. In addition, abundance of proteins involved in translation correlated with fiber hypertrophy and differed between sexes and fiber types. These findings demonstrate sex- and fiber type differences in muscle physiology and their contributions to resistance training-induced adaptions and implicate involvement of CSRP3 in resistance training-induced muscle hypertrophy.