Abstract
Changes in cardiorespiratory fitness in response to a standardized exercise training protocol differ substantially between individuals. Results from cross-sectional, twin, and family studies indicate genetics contribute to individual differences in both baseline exercise capacity and the response to training. Exercise capacity and responses to training also vary between inbred strains of mice. However, such studies have utilized a limited number of inbred strains. Therefore, the aim of this study was to characterize exercise-training responses in a larger number of genetically diverse strains of inbred mice and estimate the contribution of genetic background to exercise training responses. Eight-week old male mice from 24 inbred strains (n = 4–10/strain) performed a graded exercise test before and after 4 weeks of exercise training. Before training, exercise capacity was significantly different between strains when expressed as time (range = 21–42 min) and work performed (range = 0.42–3.89 kg·m). The responses to training also were significantly different between strains, ranging from a decrease of 2.2 min in NON/ShiLtJ mice to an increase of 8.7 min in SWR/J mice. Changes in work also varied considerably between the lowest (−0.24 kg·m in NON/ShiLtJ) and highest (+2.30 kg·m in FVB/NJ) performing strains. Heart and skeletal muscle masses also varied significantly between strains. Two broad sense heritability estimates were calculated for each measure of exercise capacity and for responses to training. For change in run time, the intraclass correlation between mice within the same inbred strain (rI) was 0.58 and the coefficient of genetic determination (g2) was 0.41. Heritability estimates were similar for the change in work: rI = 0.54 and g2 = 0.37. In conclusion, these results indicate genetic background significantly influences responses to exercise training.
Highlights
IntroductionCardiorespiratory fitness (i.e., endurance exercise capacity determined by a graded treadmill test) is a predictor of cardiovascular disease and all-cause mortality in men and women (Blair et al, 1989; Myers et al, 2002; Gulati et al, 2003; Kodama et al, 2009)
Cardiorespiratory fitness is a predictor of cardiovascular disease and all-cause mortality in men and women (Blair et al, 1989; Myers et al, 2002; Gulati et al, 2003; Kodama et al, 2009)
Strain distributions for pre-training exercise capacity expressed as time and work are shown in Figures 1A, 2A, respectively
Summary
Cardiorespiratory fitness (i.e., endurance exercise capacity determined by a graded treadmill test) is a predictor of cardiovascular disease and all-cause mortality in men and women (Blair et al, 1989; Myers et al, 2002; Gulati et al, 2003; Kodama et al, 2009). Improvements in cardiorespiratory fitness are associated with significantly reduced risk of all-cause mortality (Blair et al, 1995; Erikssen et al, 1998; Kokkinos et al, 2010; Brawner et al, 2017). Changes in cardiorespiratory fitness in response to a standardized exercise training protocol are variable (Lortie et al, 1984; Kohrt et al, 1991; Bouchard et al, 1999; Bouchard and Rankinen, 2001). The reported percentage of individuals showing minimal or no improvements in cardiorespiratory fitness in Genetic Background Influences Training Responses response to a standardized training program ranges from 7–45% (Sisson et al, 2009; Bouchard et al, 2011; Scharhag-Rosenberger et al, 2012). Individual variation in training responses is being widely investigated, the mechanisms underlying this individual variation are not fully understood
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