Maximum aerobic performance in lines of Mus selected for high wheel-running activity: effects of selection, oxygen availability and the mini-muscle phenotype.

Department of Biology, University of California, Riverside, CA 92521, USA.
Journal of Experimental Biology (Impact Factor: 3.24). 02/2006; 209(Pt 1):115-27. DOI: 10.1242/jeb.01883
Source: PubMed

ABSTRACT We compared maximum aerobic capacity during forced exercise (VO2max) in hypoxia (PO2=14% O2), normoxia (21%) and hyperoxia (30%) of lines of house mice selectively bred for high voluntary wheel running (S lines) with their four unselected control (C) lines. We also tested for pleiotropic effects of the ;mighty mini-muscle' allele, a Mendelian recessive that causes a 50% reduction in hind limb muscle but a doubling of mass-specific aerobic enzyme activity, among other pleiotropic effects. VO2max of female mice was measured during forced exercise on a motorized treadmill enclosed in a metabolic chamber that allowed altered PO2. Individual variation in VO2max was highly repeatable within each PO2, and values were also significantly correlated across PO2. Analysis of covariance showed that S mice had higher body-mass-adjusted VO2max than C at all PO2, ranging from +10.7% in hypoxia to +20.8% in hyperoxia. VO2max of S lines increased practically linearly with PO2, whereas that of C lines plateaued from normoxia to hyperoxia, and respiratory exchange ratio (=CO2 production/VO2max) was lower for S lines. These results suggest that the physiological underpinnings of VO2max differ between the S and C lines. Apparently, at least in S lines, peripheral tissues may sustain higher rates of oxidative metabolism if central organs provide more O2. Although the existence of central limitations in S lines cannot be excluded based solely on the present data, we have previously reported that both S and C lines can attain considerably higher VO2max during cold exposure in a He-O2 atmosphere, suggesting that limitations on VO2max depend on interactions between the central and peripheral organs involved. In addition, mini-muscle individuals had higher VO2max than did those with normal muscles, suggesting that the former might have higher hypoxia tolerance. This would imply that the mini-muscle phenotype could be a good model to test how exercise performance and hypoxia tolerance could evolve in a correlated fashion, as previous researchers have suggested.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This article is devoted to the role of genetic variation and gene-exercise interactions in the biology of adaptation to exercise. There is evidence from genetic epidemiology research that DNA sequence differences contribute to human variation in physical activity level, cardiorespiratory fitness in the untrained state, cardiovascular and metabolic response to acute exercise, and responsiveness to regular exercise. Methodological and technological advances have made it possible to undertake the molecular dissection of the genetic component of complex, multifactorial traits, such as those of interest to exercise biology, in terms of tissue expression profile, genes, and allelic variants. The evidence from animal models and human studies is considered. Data on candidate genes, genome-wide linkage results, genome-wide association findings, expression arrays, and combinations of these approaches are reviewed. Combining transcriptomic and genomic technologies has been shown to be more powerful as evidenced by the development of a recent molecular predictor of the ability to increase VO2max with exercise training. For exercise as a behavior and physiological fitness as a state to be major players in public health policies will require that the role of human individuality and the influence of DNA sequence differences be understood. Likewise, progress in the use of exercise in therapeutic medicine will depend to a large extent on our ability to identify the favorable responders for given physiological properties to a given exercise regimen. © 2011 American Physiological Society. Compr Physiol 1:1603-1648, 2011.
    Comprehensive Physiology. 07/2011; 1(3):1603-48.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mice from four lines bred for high voluntary wheel activity run approximately 3-fold more revolutions per day and have elevated maximal oxygen consumption during forced treadmill exercise, as compared with four unselected control (C) lines. We hypothesized that these high runner (HR) lines would have greater treadmill endurance-running capacity. Ninety-six mice from generation 49 were familiarized with running on a motorized treadmill for 3 days. On days 4 and 5, mice were given an incremental speed test (starting at 20 m min(-1), increased 1.5 m min(-1) every 2 min) and endurance was measured as the total time or distance run to exhaustion. Blood samples were taken to measure glucose and lactate concentrations at rest during the photophase, during peak nightly wheel running, and immediately following the second endurance test. Individual differences in endurance time were highly repeatable between days (r=0.79), and mice tended to run longer on the second day (paired t-test, P<0.0001). Blood glucose following the treadmill test was low for all animals ( approximately 53 mg dl(-1)) and lactate was high ( approximately 6.5 mmol l(-1)), suggesting that exhaustion occurred. The HR lines had significantly higher endurance than the C lines (1-tailed P<0.05), whether or not body mass was used as a covariate in the analysis. The relationship between line means for wheel running and treadmill endurance differed between the sexes, reinforcing previous studies that indicate sex-specific responses to selective breeding. HR mice appear to have a higher endurance capacity than reported in the literature for inbred strains of mice or transgenics intended to enhance endurance.
    Journal of Experimental Biology 09/2009; 212(18):2908-17. · 3.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic increases in circulating corticosterone (CORT) generally suppress immune function, but it is not known whether evolved increases necessarily have similar adverse effects. Moreover, the evolution of immune function might be constrained by the sharing of signaling molecules, such as CORT, across numerous physiological systems. Laboratory house mice (Mus domesticus Linnaeus) from four replicate lines selectively bred for high voluntary wheel running (HR lines) generally had baseline circulating CORT approximately twofold higher than in four non-selected control (C) lines. To test whether elevated baseline CORT suppresses the inflammatory response in HR mice, we injected females with lipopolysaccharide (LPS). All mice injected with LPS exhibited classic signs of an inflammatory response, including sickness behavior, loss of body mass, reduced locomotor activity (i.e. voluntary wheel running), enlarged spleens and livers, elevated hematocrit and elevated inflammatory cytokines. However, as compared with C mice, the inflammatory response was not suppressed in HR mice. Our results, and those of a previous study, suggest that selective breeding for high voluntary exercise has not altered immune function. They also suggest that the effects of evolved differences in baseline CORT levels may differ greatly from effects of environmental factors (often viewed as 'stressors') that alter baseline CORT during an individual's lifetime. In particular, evolved increases in circulating levels of 'stress hormones' are not necessarily associated with detrimental suppression of the inflammatory response, presumably as a result of correlated evolution of other physiological systems (counter-measures). Our results have important implications for the interpretation of elevated stress hormones and of immune indicators in natural populations.
    Journal of Experimental Biology 05/2012; 215(Pt 10):1651-61. · 3.24 Impact Factor

Full-text (2 Sources)

Available from
May 26, 2014