A Mouse Ladder-Climb Protocol Induces Acute Anabolic Signaling and Muscle-Specific Adaptations to Resistance Training

Resistance training has been shown to activate the protein synthesis pathway, leading to muscle growth in humans. However, this type of exercise has shown equivocal results in animal studies due to the difficulty of mimicking muscle overload in vivo. This study aimed to determine whether ladder-based exercise in mice induces canonical molecular, cellular, and functional adaptations to training.

Mice performed a single exercise session or 6 weeks of training in the ladder climb. Acute responses included mTOR phosphorylation, puromycin incorporation, and mRNA levels of myogenic regulatory factors (MRF). Chronic adaptations were assessed by strength, fat-free mass, physical performance, and blood lactate levels to confirm the training load. Sarcomeric proteins were analyzed using Western blot, while histology measured muscle fiber diameter and satellite cell (SC) fusion. The SC amount was quantified by flow cytometry.

After a single exercise bout, mTOR phosphorylation increased at one and 3 h, with puromycin incorporation and MRF mRNA levels elevated at 8 h. After 6 weeks of training, the mice showed increased skeletal muscle strength and fat-free mass, with no changes in physical performance. Muscle-specific adaptations included increases in sarcomeric proteins and fiber diameters. SC adaptations were associated with an increased pool and enhanced capacity to fuse with muscle fibers.

Our results demonstrate that ladder-based resistance exercise in mice induces molecular, cellular, and functional responses that are directionally consistent with adaptations reported after human resistance training, supporting its value for investigating the molecular and cellular mechanisms underlying this training.