Maximal oxygen consumption in relation to subordinate traits in lines of house mice selectively bred for high voluntary wheel running

2006 ◽  
Vol 101 (2) ◽  
pp. 477-485 ◽  
Author(s):  
Enrico L. Rezende ◽  
Fernando R. Gomes ◽  
Jessica L. Malisch ◽  
Mark A. Chappell ◽  
Theodore Garland

We studied relations between maximal O2 consumption (V̇o2 max) during forced exercise and subordinate traits associated with blood O2 transport and cellular respiration in four lines of mice selectively bred for high voluntary wheel running (S lines) and their four nonselected control (C) lines. Previously, we reported V̇o2 max of 59 females at three Po2 (hypoxia = 14% O2, normoxia = 21%, hyperoxia = 30%). Here, we test the hypothesis that variation in V̇o2 max can be explained, in part, by hemoglobin concentration and Po2 necessary to obtain 50% O2 saturation of Hb (an estimate of Hb affinity for O2) of the blood as well as citrate synthase activity and myoglobin concentration of ventricles and gastrocnemius muscle. Statistical analyses controlled for body mass, compared S and C lines, and also considered effects of the mini-muscle phenotype (present only in S lines and resulting from a Mendelian recessive allele), which reduces hindlimb muscle mass while increasing muscle mass-specific aerobic capacity. Although S lines had higher V̇o2 max than C, subordinate traits showed no statistical differences when the presence of the mini-muscle phenotype was controlled. However, subordinate traits did account for some of the individual variation in V̇o2 max. Ventricle size was a positive predictor of V̇o2 max at all three Po2. Blood Hb concentration was a positive predictor of V̇o2 max in S lines but a negative predictor in C lines, indicating that the physiological underpinnings of V̇o2 max have been altered by selective breeding. Mice with the mini-muscle phenotype had enlarged ventricles, with higher mass-specific citrate synthase activity and myoglobin concentration, which may account for their higher V̇o2 max in hypoxia.

2003 ◽  
Vol 284 (2) ◽  
pp. R433-R443 ◽  
Author(s):  
Philippe Houle-Leroy ◽  
Helga Guderley ◽  
John G. Swallow ◽  
Theodore Garland

After 14 generations of selection for voluntary wheel running, mice from the four replicate selected lines ran, on average, twice as many revolutions per day as those from the four unselected control lines. To examine whether the selected lines followed distinct strategies in the correlated responses of the size and metabolic capacities of the hindlimb muscles, we examined mice from selected lines, housed for 8 wk in cages with access to running wheels that were either free to rotate (“wheel access” group) or locked (“sedentary”). Thirteen of twenty individuals in one selected line (line 6) and two of twenty in another (line 3) showed a marked reduction (∼50%) in total hindlimb muscle mass, consistent with the previously described expression of a small-muscle phenotype. Individuals with these “mini-muscles” were not significantly smaller in total body mass compared with line-mates with normal-sized muscles. Access to free wheels did not affect the relative mass of the mini-muscles, but did result in typical mammalian training effects for mitochondrial enzyme activities. Individuals with mini-muscles showed a higher mass-specific muscle aerobic capacity as revealed by the maximal in vitro rates of citrate synthase and cytochrome c oxidase. Moreover, these mice showed the highest activities of hexokinase and carnitine palmitoyl transferase. Females with mini-muscles showed the highest levels of phosphofructokinase, and males with mini-muscles the highest levels of pyruvate dehydrogenase. As shown by total muscle enzyme contents, the increase in mass-specific aerobic capacity almost completely compensated for the reduction caused by the “loss” of muscle mass. Moreover, the mini-muscle mice exhibited the lowest contents of lactate dehydrogenase and glycogen phosphorylase. Interestingly, metabolic capacities of mini-muscled mice resemble those of muscles after endurance training. Overall, our results demonstrate that during selection for voluntary wheel running, distinct adaptive paths that differentially exploit the genetic variation in morphological and physiological traits have been followed.


2006 ◽  
Vol 38 (Suppl 1) ◽  
pp. S12
Author(s):  
Michael S. Lustgarten ◽  
Young C. Jang ◽  
Wook Song ◽  
Yuhong Liu ◽  
Anson Pierce ◽  
...  

2000 ◽  
Vol 89 (4) ◽  
pp. 1608-1616 ◽  
Author(s):  
Philippe Houle-Leroy ◽  
Theodore Garland ◽  
John G. Swallow ◽  
Helga Guderley

Selective breeding is an important tool in behavioral genetics and evolutionary physiology, but it has rarely been applied to the study of exercise physiology. We are using artificial selection for increased wheel-running behavior to study the correlated evolution of locomotor activity and physiological determinants of exercise capacity in house mice. We studied enzyme activities and their response to voluntary wheel running in mixed hindlimb muscles of mice from generation 14, at which time individuals from selected lines ran more than twice as many revolutions per day as those from control (unselected) lines. Beginning at weaning and for 8 wk, we housed mice from each of four replicate selected lines and four replicate control lines with access to wheels that were free to rotate (wheel-access group) or locked (sedentary group). Among sedentary animals, mice from selected lines did not exhibit a general increase in aerobic capacities: no mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity was significantly ( P < 0.05) higher than in control mice. Sedentary mice from the selected lines exhibited a trend for higher muscle aerobic capacities, as indicated by higher levels of mitochondrial (cytochrome- c oxidase, carnitine palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as indicated by lactate dehydrogenase (especially in male mice). Consistent with previous studies of endurance training in rats via voluntary wheel running or forced treadmill exercise, cytochrome- c oxidase, citrate synthase, and carnitine palmitoyltransferase activity increased in the wheel-access groups for both genders; hexokinase also increased in both genders. Some enzymes showed gender-specific responses: PDH and lactate dehydrogenase increased in wheel-access male but not female mice, and glycogen phosphorylase decreased in female but not in male mice. Two-way analysis of covariance revealed significant interactions between line type and activity group; for several enzymes, activities showed greater changes in mice from selected lines, presumably because such mice ran more revolutions per day and at greater velocities. Thus genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training.


1992 ◽  
Vol 262 (1) ◽  
pp. C9-C14 ◽  
Author(s):  
K. J. Rodnick ◽  
E. J. Henriksen ◽  
D. E. James ◽  
J. O. Holloszy

It was previously found that voluntary wheel running induces an increase in the insulin-sensitive glucose transporter, i.e., the GLUT4 isoform, in rat plantaris muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). The present study was undertaken to determine whether 1) the increase in muscle GLUT4 protein is associated with an increase in maximally stimulated glucose transport activity, 2) a conversion of type IIb to type IIa or type I muscle fibers plays a role in the increase in GLUT4 protein, and 3) an increase in the GLUT1 isoform is a component of the adaptation of muscle to endurance exercise. Five weeks of voluntary wheel running that resulted in a 33% increase in citrate synthase activity induced a 50% increase in GLUT4 protein in epitrochlearis muscles of female Sprague-Dawley rats. The rate of 2-deoxy-glucose transport maximally stimulated with insulin or insulin plus contractions was increased approximately 40% (P less than 0.05). There was no change in muscle fiber type composition, evaluated by myosin ATPase staining, in the epitrochlearis. There was also no change in GLUT1 protein concentration. We conclude that an increase in GLUT4, but not of GLUT1 protein, is a component of the adaptive response of muscle to endurance exercise and that the increase in GLUT4 protein is associated with an increased capacity for glucose transport.


2014 ◽  
Vol 117 (5) ◽  
pp. 482-491 ◽  
Author(s):  
James M. Kuczmarski ◽  
Christopher R. Martens ◽  
Jahyun Kim ◽  
Shannon L. Lennon-Edwards ◽  
David G. Edwards

The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO.


2013 ◽  
pp. 361-369 ◽  
Author(s):  
R. L. SCHULTZ ◽  
E. L. KULLMAN ◽  
R. P. WATERS ◽  
H. HUANG ◽  
J. P. KIRWAN ◽  
...  

The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and β-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but was increased (P<0.05) in the WFex animals. Citrate synthase protein and gene expression were unchanged in SHHFex animals, but were increased in WFex rats (P<0.05). In the WFex animals muscle glycogen was significantly depleted after exercise (P<0.05), but not in the SHHFex group. We conclude that despite robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal muscle.


2011 ◽  
Vol 300 (2) ◽  
pp. E327-E340 ◽  
Author(s):  
Chikwendu Ibebunjo ◽  
John K. Eash ◽  
Christine Li ◽  
QiCheng Ma ◽  
David J. Glass

Declines in skeletal muscle size and strength, often seen with chronic wasting diseases, prolonged or high-dose glucocorticoid therapy, and the natural aging process in mammals, are usually associated with reduced physical activity and testosterone levels. However, it is not clear whether the decline in testosterone and activity are causally related. Using a mouse model, we found that removal of endogenous testosterone by orchidectomy results in an almost complete cessation in voluntary wheel running but only a small decline in muscle mass. Testosterone replacement restored running behavior and muscle mass to normal levels. Orchidectomy also suppressed the IGF-I/Akt pathway, activated the atrophy-inducing E3 ligases MuRF1 and MAFBx, and suppressed several energy metabolism pathways, and all of these effects were reversed by testosterone replacement. The study also delineated a distinct, previously unidentified set of genes that is inversely regulated by orchidectomy and testosterone treatment. These data demonstrate the necessity of testosterone for both speed and endurance of voluntary wheel running in mice and suggest a potential mechanism for declined activity in humans where androgens are deficient.


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