Voluntary Exercise and Its Effects on Body Composition Depend on Genetic Selection History

Abstract

Little is known about how genetic variation affects the capacity for exercise to change body composition. We examined the extent to which voluntary exercise alters body composition in several lines of selectively bred mice compared to controls. Lines studied included high runner (HR) (selected for high wheel running), M16 (selected for rapid weight gain), Institute of Cancer Research (ICR) (randomly bred as control for M16), M16i (an inbred line derived from M16), HE (selected for high percentage of body fat while holding body weight constant), LF (selected for low percentage of body fat), C57BL/6J (common inbred line), and the F1 between HR and C57BL/6J. Body weight and body fat were recorded before and after 6 days of free access to running wheels in males and females that were individually caged. Total food intake was measured during this 6‐day period. All pre‐ and postexercise measures showed significant strain effects. While HR mice predictably exercised at higher levels, all other selection lines had decreased levels of wheel running relative to ICR. The HR × B6 F1 ran at similar levels to HR demonstrating complete dominance for voluntary exercise. Also, all strains lost body fat after exercise, but the relationships between exercise and changes in percent body were not uniform across genotypes. These results indicate that there is significant genetic variation for voluntary exercise and its effects on body composition. It is important to carefully consider genetic background and/or selection history when using mice to model effects of exercise on body composition, and perhaps, other complex traits as well.

The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives

“…Results to date make it clear that the effects of physical activity on the human body mass index (BMI) vary with genotype , and similar results have been observed for different strains of mice (Nehrenberg et al, 2009a;Meek et al, 2010 For a review of the measurement of physical activity in humans, see Westerterp (Westerterp, 2009). Note that both voluntary exercise and spontaneous activity can be quantified in terms of duration, intensity or total activity (product of duration and intensity).…”

“…Further, the increase in endurance by lines of mice bred for high voluntary wheel running (Meek et al, 2009) and the divergence in wheel running of two rat lines bred for high or low endurance capacity indicate that exercise propensity and ability are positively genetically correlated in these rodents. [Based on mouse selection experiments, Nehrenberg et al have suggested that physical activity and body composition are negatively genetically correlated (Nehrenberg et al, 2009a).] Finally, these same lines show parallel differences in SPA, body size, percent body fat and circulating leptin levels when housed without wheels (Girard et al, 2007;Malisch et al, 2009;Meek et al, 2010;Novak et al, 2009;Novak et al, 2010) (T.G., H.S., M.A.C., T.H.M., L.E.C., W.A.…”

“…Another factor adding complexity is that genotype-environment interactions are likely to be common (see also Dishman, 2008). For example, the relationships between physical activity, energy intake and body composition can differ dramatically between the sexes, among individual humans and among strains of mice, and the effects of exercise training are also known to vary among individual humans in relation to genotype Melzer et al, 2005;Girard et al, 2007;Vaanholt et al, 2008;Nehrenberg et al, 2009a;Jung and Luthin, 2010;Jung et al, 2010;Meek et al, 2010;Timmons et al, 2010). As noted in the previous section, wheel access usually, but not always, reduces body fat in rodents, especially in males.…”

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

“…Previous studies have also found that HR mice have less body fat than C mice, and even a lower % body fat than mice from a separate experiment that selectively bred for low body fat. 23 Reanalysis of mice from generation 14 (data from Houle-Leroy et al 24 ) indicates HR males have elevated carnitine palmitoyltransferase levels compared to C lines, suggesting a higher ability to oxidize fats. 9 Therefore, we hypothesized that insufficient dietary lipids may be one factor limiting further evolutionary increases in wheel running by the HR lines.…”

Erythropoietin elevates but not voluntary wheel running in mice

“…[Interestingly, HR mice also exhibit elevated home-cage activity when housed without access to running wheels (Malisch et al, 2008;Malisch et al, 2009)]. Instead, the reduced body fat (Swallow et al, 2001;Nehrenberg et al, 2009), reduced circulating leptin levels (Girard et al, 2007) (but see Vaanholt et al, 2008) and increased circulating adiponectin levels [(Vaanholt et al, 2007b) depending on sex and diet (Vaanholt et al, 2008)], suggest that lipid availability may be a limiting factor (see also Gomes et al, 2009). However, recent work in human 'ultraendurance' athletes (Pearson, 2006) suggests that neurobiological attributes make a greater contribution to performance than has previously been acknowledged (Kayser, 2003;Baden et al, 2005;Noakes, 2007;Rose and Parfitt, 2007;Noakes, 2009) …”