Intrastrain Variation in Exercise Trainability is Linked to Changes in Body Weight in HET3 Mice

Abstract

PURPOSE: The purpose of this study was to characterize endurance trainability in the genetically heterogenous HET3 aging mouse model by assessing change in exercise capacity after completing a standardized treadmill training protocol. Secondarily, we also aimed to assess the association between exercise capacity changes with body composition measures in response to the training. METHODS: We randomly assigned 40-week-old male mice to endurance training (ET, n = 23) or sedentary control (SED, n = 20) groups. Both groups underwent a graded treadmill exercise capacity test before and after four weeks of exercise training. ET mice trained five days per week for four weeks at 65% of the maximal work output calculated in joules (J = kg*gravity*vertical speed*time). Additionally, we analyzed training-induced changes in body composition (total body weight, lean mass, and fat mass). We employed an independent sample t-test to compare changes in total work and regression analysis to assess the association between post-training exercise work and body composition measures (body weight, fat mass, and lean mass) and exercise work (alpha level = 0.05). RESULTS: While we found the mean change in exercise work was significantly greater in ET versus SED mice (ET: 483.3 ± 48.8 joules, SED: 194.7 ± 52.0 joules; p = 0.0003), there was considerable variance in change within each group (Range: ET = 74.4 - 925.4 joules; SED = 85.1 - 432.0 joules). In the ET mice, change in work was positively correlated with post-training body weight (37.3 ± 1.3 gms, p = 0.004) and the change in body weight (-9.5 ± 1.8 gms, p = 0.01) but no other pre- or post-training body composition factors. We did not find associations between body composition measures and exercise work in the untrained animals. CONCLUSIONS: While the standardized treadmill training protocol increased exercise capacity in HET3 ET mice, these changes were variable. Interestingly, greater declines in body weight with training were associated with lower exercise capacity that was not linked to pre-training body weight, possibly suggesting food consumption and/or spontaneous cage activity may have influenced results. Taken together, the variable responses in exercise capacity and factors contributing to change in body weight may be, at least partially, explained by their heterogeneous nature.