Effects of voluntary activity and genetic selection on muscle metabolic capacities in house mice Mus domesticus

2000 ◽  
Vol 89 (4) ◽  
pp. 1608-1616 ◽  
Author(s):  
Philippe Houle-Leroy ◽  
Theodore Garland ◽  
John G. Swallow ◽  
Helga Guderley
Keyword(s):  
Lactate Dehydrogenase ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Genetic Selection ◽  
House Mice ◽  
Male Mice ◽  
Selected Lines ◽  
Voluntary Wheel Running ◽  
Selection For ◽  
Voluntary Wheel

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.

Artificial selection for high activity favors mighty mini-muscles in house mice

2003 ◽  
Vol 284 (2) ◽  
pp. R433-R443 ◽  
Author(s):  
Philippe Houle-Leroy ◽  
Helga Guderley ◽  
John G. Swallow ◽  
Theodore Garland
Keyword(s):  
Muscle Mass ◽  
Aerobic Capacity ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Relative Mass ◽  
Selected Lines ◽  
Voluntary Wheel Running ◽  
Total Body Mass ◽  
Selection For ◽  
Voluntary Wheel

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.

Selection for high voluntary wheel-running increases speed and intermittency in house mice (Mus domesticus)

2001 ◽  
Vol 204 (24) ◽  
pp. 4311-4320 ◽  
Author(s):  
I. Girard ◽  
M. W. McAleer ◽  
J. S. Rhodes ◽  
T. Garland
Keyword(s):  
Intermittent Exercise ◽  
Wheel Running ◽  
House Mice ◽  
Mus Domesticus ◽  
Selection Line ◽  
Control Line ◽  
Voluntary Wheel Running ◽  
Continuous Exercise ◽  
Selection For ◽  
Voluntary Wheel

SUMMARY In nature, many animals use intermittent rather than continuous locomotion. In laboratory studies, intermittent exercise regimens have been shown to increase endurance compared with continuous exercise. We hypothesized that increased intermittency has evolved in lines of house mice (Mus domesticus) that have been selectively bred for high voluntary wheel-running (wheel diameter 1.12 m) activity. After 23 generations, female mice from four replicate selection lines ran 2.7 times more revolutions per day than individuals from four random-bred control lines. To measure instantaneous running speeds and to quantify intermittency, we videotaped mice (N=41) during a 5-min period of peak activity on night 6 of a 6-day exposure to wheels. Compared with controls (20 revs min–1 while actually running), selection-line females (41 revs min–1) ran significantly faster. These instantaneous speeds closely matched the computer-recorded speeds over the same 5-min period. Selection-line females also ran more intermittently, with shorter (10.0 s bout–1) and more frequent (7.8 bouts min–1) bouts than controls (16.8 s bout–1, 3.4 bouts min–1). Inter-bout pauses were also significantly shorter in selection-line (2.7 s) than in control-line (7.4 s) females. We hypothesize that intermittency of locomotion is a key feature allowing the increased wheel-running performance at high running speeds in selection-line mice.

Artificial selection for increased wheel-running activity in house mice results in decreased body mass at maturity

1999 ◽  
Vol 202 (18) ◽  
pp. 2513-2520 ◽  
Author(s):  
J.G. Swallow ◽  
P. Koteja ◽  
P.A. Carter ◽  
T. Garland
Keyword(s):  
Genetic Correlation ◽  
Body Mass ◽  
Artificial Selection ◽  
Wheel Running ◽  
House Mice ◽  
Selected Lines ◽  
Voluntary Wheel Running ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Voluntary Wheel

To test the hypothesis that body size and activity levels are negatively genetically correlated, we conducted an artificial selection experiment for increased voluntary wheel-running activity in house mice (Mus domesticus). Here, we compare body masses of mice from control and selected lines after 14 generations of selection. In both groups, beginning at weaning and then for 8 weeks, we housed half of the individuals with access to running wheels that were free to rotate and the other half with wheels that were locked to prevent rotation. Mice from selected lines were more active than controls at weaning (21 days) and across the experiment (total revolutions during last week: females 2.5-fold higher, males 2.1-fold higher). At weaning, mice from selected and control lines did not differ significantly in body mass. At 79 days of age, mice from selected lines weighed 13.6 % less than mice from control lines, whereas mice with access to free wheels weighed 4.5 % less than ‘sedentary’ individuals; both effects were statistically significant and additive. Within the free-wheel-access group, individual variation in body mass of males was negatively correlated with amount of wheel-running during the last week (P&lt;0.01); for females, the relationship was also negative but not statistically significant (P&gt;0.40). The narrow-sense genetic correlation between wheel-running and body mass after 8 weeks of wheel access was estimated to be −0. 50. A negative genetic correlation could account for the negative relationship between voluntary wheel-running and body mass that has been reported across 13 species of muroid rodents.

Contractile abilities of normal and “mini” triceps surae muscles from mice (Mus domesticus) selectively bred for high voluntary wheel running

2005 ◽  
Vol 99 (4) ◽  
pp. 1308-1316 ◽  
Author(s):  
Douglas A. Syme ◽  
Kristin Evashuk ◽  
Benjamin Grintuch ◽  
Enrico L. Rezende ◽  
Theodore Garland
Keyword(s):  
Wheel Running ◽  
Fold Increase ◽  
Triceps Surae ◽  
Medial Gastrocnemius ◽  
Selected Lines ◽  
Voluntary Wheel Running ◽  
Running Activity ◽  
Gastrocnemius Muscles ◽  
Contractile Characteristics ◽  
Voluntary Wheel

As reported previously, artificial selection of house mice caused a 2.7-fold increase in voluntary wheel running of four replicate selected lines compared with four random-bred control lines. Two of the selected lines developed a high incidence of a small-muscle phenotype (“mini muscles”) in the plantar flexor group of the hindlimb, which apparently results from a simple Mendelian recessive allele. At generations 36–38, we measured wheel running and key contractile characteristics of soleus and medial gastrocnemius muscles from normal and mini muscles in mice from these selected lines. Mice with mini muscles ran faster and a greater distance per day than normal individuals but not longer. As expected, in mini-muscle mice the medial and lateral gastrocnemius muscles were ∼54 and 45% the mass of normal muscles, respectively, but the plantaris muscles were not different in mass and soleus muscles were actually 30% larger. In spite of the increased mass, contractile characteristics of the soleus were unchanged in any notable way between mini and normal mice. However, medial gastrocnemius muscles in mini mice were changed markedly toward a slower phenotype, having slower twitches; demonstrated a more curved force-velocity relationship; produced about half the mass-specific isotonic power, 20–50% of the mass-specific cyclic work and power (only 10–25% the absolute power if the loss in mass is considered); and fatigued at about half the rate of normal muscles. These changes would promote increased, aerobically supported running activity but may compromise activities that require high power, such as sprinting.

Exercise training, glucose transporters, and glucose transport in rat skeletal muscles

1992 ◽  
Vol 262 (1) ◽  
pp. C9-C14 ◽  
Author(s):  
K. J. Rodnick ◽  
E. J. Henriksen ◽  
D. E. James ◽  
J. O. Holloszy
Keyword(s):  
Glucose Transport ◽  
Endurance Exercise ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Fiber Type ◽  
Type I ◽  
Voluntary Wheel Running ◽  
Glut1 Protein ◽  
Voluntary Wheel

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.

scholarly journals Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease

2014 ◽  
Vol 117 (5) ◽  
pp. 482-491 ◽  
Author(s):  
James M. Kuczmarski ◽  
Christopher R. Martens ◽  
Jahyun Kim ◽  
Shannon L. Lennon-Edwards ◽  
David G. Edwards
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Voluntary Wheel Running ◽  
Low Volume ◽  
Voluntary Wheel

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.

scholarly journals Artificial Selection for Increased Voluntary Wheel Running Alters Limb Skeleton Shape and Exercise Plasticity in Mice

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Amanda N Smolinsky ◽  
Kristina Aldridge ◽  
Alberto A Castro ◽  
Theodore Garland ◽  
Kevin M Middleton
Keyword(s):  
Artificial Selection ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Selection For ◽  
Voluntary Wheel

scholarly journals Metabolic Adaptations of Skeletal Muscle to Voluntary Wheel Running Exercise in Hypertensive Heart Failure Rats

2013 ◽  
pp. 361-369 ◽  
Author(s):  
R. L. SCHULTZ ◽  
E. L. KULLMAN ◽  
R. P. WATERS ◽  
H. HUANG ◽  
J. P. KIRWAN ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Heart Function ◽  
Oxidative Capacity ◽  
Voluntary Wheel Running ◽  
Spontaneously Hypertensive ◽  
Running Exercise ◽  
Voluntary Wheel

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.

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