Selectively bred rat model system for low and high response to exercise training

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.

Mitochondrial biogenesis-associated factors underlie the magnitude of response to aerobic endurance training in rats

“…In conclusion, these rat models of low response trainers (LRT) and high response trainers (HRT) represent the first heterogeneous substrate that can serve as reagents towards understanding the molecular networks responsible for variation in trainability [19]. Our data suggest: 1) Baseline levels of VO 2 max do not strongly affect the adaptive response to aerobic exercise training.…”

“…Low response trainers (LRT) and high response trainers (HRT) were developed by selective breeding and are maintained as a contrasting animal model system at the University of Michigan by Koch and Britton [19]. Twenty-seven male rats from the 11 th generation of selection, 13 LRT and 14 HRT, were studied.…”

“…Recently an animal model system was developed via artificial selective breeding, which permits researchers to study the inherited components of low and high trainability in rats [19]. This model was set up using a genetically heterogeneous rat population (N/NIH stock) to develop lines named low response trainers (LRT) and high response trainers (HRT) [19]. Selection was based on the change in maximal running distance evaluated by a treadmill-running test to exhaustion.…”

“…In the untrained condition, LRT and HRT rats are similar for exercise capacity. However after receiving 8 weeks of a standard amount of endurance training, HRT rats improve on average by 200 meters for distance run whereas those bred as LRT failed to improve and on average, declined in running capacity by −65 meters [19]. A recent study by Lessard et al [23] showed that skeletal muscle mitochondrial capacity was similar between LRT and HRT in the sedentary state and that LRT produced normal increases in mitochondrial density and function in response to moderate intensity endurance training.…”

“Weighing” the effects of exercise and intrinsic aerobic capacity: are there beneficial effects independent of changes in weight?

“…In addition, the HCR and LCR display traits that uniquely model low and high-fitness human subjects, including that the LCR display obesity, cardiovascular risk factors, and fatty liver at a relatively young age (20–30 weeks) on a normal chow diet (Thyfault et al 2009), display earlier mortality (∼6 months) (Koch et al 2011) than high-fitness HCR rats, and are more susceptible to a variety of disease conditions (as reviewed in Garton et al (2016)). Britton and Koch have continued to breed the HCR and LCR over 30 generations and information related to running capacity and genetics are reported elsewhere (Koch et al 2013; Ren et al 2013). …”