Endurance and Resistance Exercise Muscle Memory Differentially Impact Muscle Growth and Mitochondrial Metabolism

Skeletal muscle is a highly plastic tissue that responds to specific stimuli, including different exercise modalities, which include endurance- or resistance-based training. This is of particular importance given the newfound interest in the muscle memory, or the the long-term, persistent adaptations to prior exercise training. Here, we aimed to investigate how exercise modalities differentially prime the muscle memory. Using novel endurance- (Voluntary Wheel Running; VWR) or resistance-based exercise protocols (PoWeR; progressive weighted VWR of up to 15g added weight), we probed the memory following successive 4wk-TRAINing, 4wk-DETRAINing, and 4wk-RETRAINing cycles. We hypothesize that prior exercise TRAINing induces mitochondrial adaptations resulting in muscle growth which persist through time and are potentiated to improve muscle function. We assessed body composition, muscle fiber type and size (immunofluorescence), transcriptomics (bulk RNA-seq), and protein levels (immunoblot) after each TRAIN, DETRAIN, and RETRAIN cycle. Endurance (VWR) and resistance (PoWeR) TRAINing showed similar reductions in fat mass and comparable increases in adiposity after DETRAINing, but PoWeR RETRAINing resulted in greater body weight loss. Hindlimb muscles showed increased growth following RETRAINing, with VWR producing greater effect sizes in the tibialis anterior, gastrocnemius, and plantaris muscles compared to TRAINing alone. Importantly, both VWR and PoWeR similarly enhanced the growth of the soleus muscle following RETRAINing. Plantaris muscle fiber analysis showed PoWeR TRAINing increased fiber cross-sectional area (fCSA) in all fiber types, whereas VWR TRAINing only increased size of oxidative fibers. However, with RETRAINing, both VWR and PoWeR increased fCSA of oxidative and intermediate fibers. PoWeR, but not VWR, TRAINing altered fiber type distribution to more oxidative and less glycolytic fibers, which disappeared with DETRAINing and returned with RETRAINing. This is in line with our muscle transcriptomic analysis, showing a marked enhancement of nuclear-encoded mitochondrial genes after RETRAINing. Further, PoWeR TRAINing produced similar increases in fatty acid oxidation protein CPT1B and the oxidative phosphorylation complexes (OxPhos) but were reduced following RETRAINing. Conversely, VWR RETRAINing significantly increased expression of CPT1B and OxPhos complex IV, indicating diverging effects on mitochondrial protein abundance. Altogether, our novel exercise training protocols resulted in similar muscle memory recall of prior exercise adaptations. The effects of PoWeR appear to be more intense than VWR, reducing body weight to a greater extent while maintaining lean body mass. Both exercise modalities result in similar muscle growth during TRAINing but differ during RETRAINing, with PoWeR having a greater impact on fiber distribution. These adaptations appear to be linked to diverging effects on mitochondrial metabolism which may be leveraged to enhance muscle health and function. Funding was provided by the Center for Healthy Aging and Disability at the University of Illinois Urbana-Champaign. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.