Effects of physical activity reduction on the gastrocnemius transcriptome

Insufficient physical activity is associated with increased relative risk of cardiometabolic disease and is an independent risk factor for mortality. Experimentally reducing physical activity rapidly induces insulin resistance, impairs glucose handling, and drives metabolic inflexibility. These adaptations manifest during the early stages of physical inactivity, even when energy balance is maintained, suggesting that inactivity-mediated metabolic reprogramming is an early event that precedes changes in body composition. To identify mechanisms that promote metabolic adaptations associated with physical inactivity, we developed a mouse model of physical activity reduction that permits the study of inactivity in animals prior to the onset of overt changes in body composition. Adult mice were randomized into three groups: an inactive control group (standard housing), an active control group (treadmill running for 6-weeks), and an activity reduction group (treadmill running for 4-weeks, followed by 2-weeks of inactivity). Transcriptional profiling of gastrocnemius muscle was performed. Overall design: 10 week old female C57BL6/NJ mice either remained sedentary (standard housing and enrichment), treadmill trained 5 d/week for 40 min/session at 70% of maximal running speed for 6 weeks, or treadmill trained for 4 weeks followed by 2 weeks of inactivity. Tissues were collected in the 5-6 h fasted state after 48-72 h had passed since the final exercise session (which was a maximal running test that all mice regardless of group assignment undertook).