Abstract
We initiated a large-scale bidirectional selection experiment in a genetically heterogeneous rat population (N/NIH stock, n = 152) to develop lines of low response trainers (LRT) and high response trainers (HRT) as a contrasting animal model system. Maximal treadmill running distance [meters (m)] was tested before (DIST(1)) and after (DIST(2)) standardized aerobic treadmill training over an 8 wk period (3 exercise sessions per week). Response to training was calculated as the change in exercise capacity (ΔDIST = DIST(2) - DIST(1)). A within-family selection and rotational breeding paradigm between 10 families was practiced for both selected lines. For the founder population, exercise training produced a 140 ± 15 m gain in exercise capacity with interindividual variation ranging from -339 to +627 m. After 15 generations of selection (n = 3,114 rats), HRT rats improved 223 ± 20 m as a result of exercise training while exercise capacity declined -65 ± 15 m in LRT rats given the same absolute training environment. The narrow-sense heritability (h(2)) for ΔDIST was 0.10 ± 0.02. The LRT and HRT lines did not differ significantly for body weight or intrinsic (i.e., DIST(1)) exercise capacity. Using pedigree records the inbreeding coefficient increased at a rate of 1.7% per generation for HRT and 1.6% per generation for LRT, ∼30% slower than expected from random mating. Animal models developed from heterogeneous stock and enriched via selection, as presented here, often generate extreme values for traits of interest and may prove more useful than current models for uncovering genetic underpinnings.
Highlights
LOW AEROBIC EXERCISE CAPACITY is linked to a higher probability of harboring elevated complex disease risks and lower survivability [2, 4, 11, 18, 34, 37]
The DIST2 showed completely the opposite in that the two lines diverged at both the phenotypic and genetic levels (Fig. 4B). We found both the phenotypic and estimated breeding value (EBV) changes for body weight before (BWT1) and after training (BWT2) over the generations to be small; the high response trainers (HRT) line tended to be slightly lighter than the low response trainers (LRT) line (i.e., ϳ20 g difference in EBV between LRT and HRT selected lines; data not shown)
The strong statistical association between exercise capacity and survival suggests a link between impaired aerobic energy transfer and disease risk [49]
Summary
LOW AEROBIC EXERCISE CAPACITY is linked to a higher probability of harboring elevated complex disease risks and lower survivability [2, 4, 11, 18, 34, 37]. As an initial strategy in previous work, we first modeled the intrinsic component of exercise capacity by divergent selection on the inborn capacity for endurance treadmill running in rats in the untrained condition [30] The development of this first model provided a direct test of our general hypothesis that a diminished capacity for aerobic energy transfer underlies complex disease risks at all levels of biological organization (aerobic hypothesis) [29]. We reasoned that two-way artificial selection on the magnitude of change in running capacity (⌬DIST) as a result of training across several generations would yield a contrasting animal model system and serve as unique substrate to uncover genetic features responsible for low and high responsiveness to exercise training. We report here progress across 15 generations of artificial selective breeding that produced contrasting lines of low response trainers (LRT) and high response trainers (HRT)
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