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: 2.9). 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.

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Available from: Theodore Garland, Sep 29, 2015
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    • ". The speed was increased by 15 cm s −1 every 45 s until the mice were unable to maintain the effort level (Rezende et al. 2006). "
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    ABSTRACT: Endurance exercise training as well as leucine supplementation modulates glucose homeostasis and protein turnover in mammals. Here, we analyze whether leucine supplementation alters the effects of endurance exercise on these parameters in healthy mice. Mice were distributed into sedentary (C) and exercise (T) groups. The exercise group performed a 12-week swimming protocol. Half of the C and T mice, designated as the CL and TL groups, were supplemented with leucine (1.5 % dissolved in the drinking water) throughout the experiment. As well known, endurance exercise training reduced body weight and the retroperitoneal fat pad, increased soleus mass, increased VO2max, decreased muscle proteolysis, and ameliorated peripheral insulin sensitivity. Leucine supplementation had no effect on any of these parameters and worsened glucose tolerance in both CL and TL mice. In the soleus muscle of the T group, AS-160(Thr-642) (AKT substrate of 160 kDa) and AMPK(Thr-172) (AMP-Activated Protein Kinase) phosphorylation was increased by exercise in both basal and insulin-stimulated conditions, but it was reduced in TL mice with insulin stimulation compared with the T group. Akt phosphorylation was not affected by exercise but was lower in the CL group compared with the other groups. Leucine supplementation increased mTOR phosphorylation at basal conditions, whereas exercise reduced it in the presence of insulin, despite no alterations in protein synthesis. In trained groups, the total FoxO3a protein content and the mRNA for the specific isoforms E2 and E3 ligases were reduced. In conclusion, leucine supplementation did not potentiate the effects of endurance training on protein turnover, and it also reduced its positive effects on glucose homeostasis.
    Amino Acids 01/2015; 47(4). DOI:10.1007/s00726-014-1903-z · 3.29 Impact Factor
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    • "During exercise withdrawal (removal of wheels following several days of access), HR mice exhibit altered brain activity ([47]; only females were studied) and elevated behavioral despair ([16]; males only). HR mice have larger heart ventricular mass than C mice [48] [49], which could have implications for stroke volume, cardiac output, and BP. Likewise, elevated blood hemoglobin concentrations following injection of an erythropoietin (EPO) analog are associated with a larger spleen mass in both line types [49]. "
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    ABSTRACT: Exercise is known to be rewarding and have positive effects on mental and physical health. Excessive exercise, however, can be the result of an underlying behavioral/physiological addiction. Both humans who exercise regularly and rodent models of exercise addiction sometimes display behavioral withdrawal symptoms, including depression and anxiety, when exercise is denied. However, few studies have examined the physiological state that occurs during this withdrawal period. Alterations in blood pressure (BP) are common physiological indicators of withdrawal in a variety of addictions. In this study, we examined exercise withdrawal in four replicate lines of mice selectively bred for high voluntary wheel running (HR lines). Mice from the HR lines run almost 3-fold greater distances on wheels than those from non-selected control lines, and have altered brain activity as well as increased behavioral despair when wheel access is removed. We tested the hypothesis that male HR mice have an altered cardiovascular response (heart rate, systolic, diastolic, and mean arterial pressure [MAP]) during exercise withdrawal. Measurements using an occlusion tail-cuff system were taken during 8days of baseline, 6days of wheel access, and 2days of withdrawal (wheel access blocked). During withdrawal, HR mice had significantly lower systolic BP, diastolic BP, and MAP than controls, potentially indicating a differential dependence on voluntary wheel running in HR mice. This is the first characterization of a cardiovascular withdrawal response in an animal model of high voluntary exercise.
    Physiology & Behavior 02/2013; 112. DOI:10.1016/j.physbeh.2013.02.010 · 2.98 Impact Factor
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    • "Selection criterion/ method/species BMR response Correlated traits Trait response Reference Mass-corrected BMR/ indirect calorimetry/ laboratory mice (Mus musculus) Increase Food consumption Increase Ksia ˛ _ zek et al. (2009) Voluntary activity Increase Ge ˛bczyn´ski and Konarzewski (2009) VO 2max (treadmill) No change VO 2max (swim elicited) Decrease Ksia ˛ _ zek et al. (2004) Brze ˛k et al. (2007) Core body temperature No change Ge ˛bczyn´ski (2008) Brze ˛k et al. (2012) Mass of heart, liver, kidney, small intestine Increase Ksia ˛ _ zek et al. (2004) Ge ˛bczyn´ski and Konarzewski (2011) Fat mass Decrease Ksia ˛ _ zek et al. (2004) BAT mass Decrease Erythrocyte size Decrease Maciak et al. (2011) Immune response (SRBC) Decrease Ksia ˛ _ zek et al. (2003) Immune response (KLH) Increase Ksia ˛ _ zek and Konarzewski (2012) Mass of spleen and lymph nodes Increase Thymus mass Decrease Oxidative enzyme capacity Increase Ksia ˛ _ zek et al. (2009) Unsaturation index of cell membranes Decrease Brze ˛k et al. (2007) Mass-corrected food intake/ laboratory mice (Mus musculus) Increase Digestive efficiency Increase Hastings et al. (1997) Fat mass Decrease Bunger et al. (1998) Core body temperature No change Hambly et al. (2005) Liver mass (dry) Increase Small intestine length (fresh) Increase Small intestine mass (dry) No change Selman et al. (2001a, b) Large intestine mass (dry) Decrease Pancreas mass (dry) No change Stomach mass (dry) Increase Kidneys mass (dry) No change Heart mass (dry) Increase Lung mass (dry) No change Brain mass (dry) Increase Thyroid mass (dry) Decrease Spleen mass (dry) No change Heat loss/(body mass) 0.75 /direct calorimetry/laboratory mice (Mus musculus) Not measured Food consumption Increase Nielsen et al. (1997b) Voluntary locomotor activity Increase Nielsen et al. (1997a) Mass of liver, heart, spleen Increase Moody et al. (1999) Core body temperature Increase Mousel et al. (2001) T4 level Decrease Kgwatalala and Nielsen (2004) T3 level No change Corticosterone level Increase Expression of UCP-1 Decrease McDaneld et al. (2002) Table 1 continued Selection criterion/ method/species BMR response Correlated traits Trait response Reference Mass-corrected VO 2max / swimming/laboratory mice (Mus musculus) No change Heart mass Increase Ge ˛bczyn´ski and Konarzewski (2009) Mass of liver, kidney, small intestine No change Mass of gastrocnemius Increase Aerobic endurance capacity/ treadmill running/rats (Rattus norvegicus) Not measured Body mass Decrease Koch and Britton (2001) Fat mass Decrease Kirkton et al. (2009) VO 2max Increase Henderson et al. (2002) Mass of heart, lung, liver, kidney, stomach Increase Swallow et al. (2010) Cardiac output Increase Pulmonary function Increase Howlett et al. (2003) Oxidative enzyme capacity Increase Left ventricular cells systolic and diastolic function Increase Small intestine length Decrease Wislöff et al. (2005) Capillary density Increase Henderson et al. (2002) Mitochondrial biogenesis Increase Gonzales et al. (2006) Oxidative enzyme capacity Increase Wislöff et al. (2005) Voluntary locomotor activity/daily wheel running activity/laboratory mice (Mus musculus) No change VO 2max Increase Swallow et al. (1998) Rezende et al. (2006a, b, c) Kane et al. (2008) "
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    ABSTRACT: Basal metabolic rate (BMR) provides a widely accepted benchmark of metabolic expenditure for endotherms under laboratory and natural conditions. While most studies examining BMR have concentrated on inter-specific variation, relatively less attention has been paid to the determinants of within-species variation. Even fewer studies have analysed the determinants of within-species BMR variation corrected for the strong influence of body mass by appropriate means (e.g. ANCOVA). Here, we review recent advancements in studies on the quantitative genetics of BMR and organ mass variation, along with their molecular genetics. Next, we decompose BMR variation at the organ, tissue and molecular level. We conclude that within-species variation in BMR and its components have a clear genetic signature, and are functionally linked to key metabolic process at all levels of biological organization. We highlight the need to integrate molecular genetics with conventional metabolic field studies to reveal the adaptive significance of metabolic variation. Since comparing gene expressions inter-specifically is problematic, within-species studies are more likely to inform us about the genetic underpinnings of BMR. We also urge for better integration of animal and medical research on BMR; the latter is quickly advancing thanks to the application of imaging technologies and 'omics' studies. We also suggest that much insight on the biochemical and molecular underpinnings of BMR variation can be gained from integrating studies on the mammalian target of rapamycin (mTOR), which appears to be the major regulatory pathway influencing the key molecular components of BMR.
    Journal of Comparative Physiology B 07/2012; 183(1). DOI:10.1007/s00360-012-0698-z · 2.62 Impact Factor
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