Maximum cold-induced food consumption in mice selected for high locomotor activity: implications for the evolution of endotherm energy budgets

2001 ◽  
Vol 204 (6) ◽  
pp. 1177-1190 ◽  
Author(s):  
P. Koteja ◽  
J.G. Swallow ◽  
P.A. Carter ◽  
T. Garland

We studied house mice (Mus domesticus) that had been artificially selected for high activity to test the hypothesis that a high capacity for energy assimilation in cold-exposed endotherms could evolve as a correlated response to selection for increased locomotor activity. After 10 generations of selection for increased voluntary wheel-running, mice from four selected lines ran 75 % more wheel revolutions per day than did mice from four random-bred, control lines. The maximum cold-induced rates of food consumption (C(max); mean 10.6 g day(−1)) and energy assimilation (A(max); mean 141 kJ day(−1)) were not significantly higher in the selected than in the control mice. However, in cold-exposure trials, mice from the selected lines maintained body mass better than did mice from the control lines. C(max) and A(max) were positively correlated with the amount of wheel-running activity measured before cold-exposure and also with the rates of food consumption measured when the mice had access to running wheels. In females at least, the correlation was significant not only among individuals but also among adjusted means of the replicate lines, which suggests the presence of a positive genetic correlation between the traits. Thus, despite the lack of a significant difference between the selected and control lines in maximum rate of food consumption, the remaining results conform to the hypothesis that a selection for increased locomotor activity could be a factor behind the evolution of the ability to sustain activity and maintain energy balance during prolonged cold-exposure, as occurred during the evolution of mammalian and avian endothermy.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 10-10
Author(s):  
Leorey Saligan

10 Background: Fatigue is a common symptom characterized by incapacitating tiredness. Androgen deprivation therapy (ADT) in combination with radiotherapy (RT) is one of the standard treatments for prostate cancer. Fatigue often worsens during RT with concomitant ADT and it persists long after treatment completion. The purpose of this study is to examine the effects of combined ADT and RT on fatigue in prostate cancer men and in a fatigue mouse model. Methods: 64 participants were recruited and followed at baseline, midpoint, completion, and 1 year post-RT. Two cohorts of men: +ADT cotinued after RT (n=27), +ADT during RT only (n=20), and -ADT (n=17). Fatigue was measured using FACT-F. Male C57BI/6 mice (n=55) were randomly placed into 2 groups: +ADT and –ADT (control). Mice were further subdivided into +RT and –RT (sham) groups. Voluntary Wheel Running Activity (VWRA) data from all mice were recorded for 6 days post-irradiation and the total average of all 6 days was used for analysis. Results: Fatigue (n=64) worsened during RT ( p=.02 at midpoint, p=.04 at completion). ADT significantly affected fatigue development over time (F3,42 = 3.80, p=.02) with the most significant difference occurring at midpoint ( p<.001) and completion of RT ( p<0.001). VWRA significantly decreased in mice that received the combination of ADT and irradiation, compared to those that received only ADT + sham radiation ( p=.001) and no ADT + sham radiation ( p=.004). Transcription factor A, mitochondrial (TFAM) in brain cortical samples was significantly reduced in irradiated mice compared to control mice ( p=.014). Glucose transported type 4 (GLUT4) in brain cortices was significantly reduced in irradiated mice compared to non-irradiated mice ( p=.0057). GLUT4 was also significantly reduced in irradiated mice receiving ADT compared to control mice receiving sham RT ( p=.043). Conclusions: There is a significant combined effect of ADT and RT on fatigue in both humans and mice. Mitochondrial function/neuronal bioenergetic markers were altered in the cortices of irradiated mice that received concomitant ADT. These findings suggest that fatigue experienced by subjects who receive ADT + RT could be attributable to impaired cortical energy production.


1985 ◽  
Vol 248 (3) ◽  
pp. R320-R330 ◽  
Author(s):  
G. S. Richardson ◽  
M. C. Moore-Ede ◽  
C. A. Czeisler ◽  
W. C. Dement

Circadian rhythms of wheel-running activity and polygraphically defined wakefulness, rapid-eye-movement (REM) sleep and non-REM (NREM) sleep were continuously observed in ten mice (Mus musculus) under both alternating light-dark (LD 12:12) and continuous darkness (DD) conditions. Sleep-wake state was determined automatically using a computer-based method that allowed continuous recordings of from 60 to 280 days in duration. The sleep-wake state percentages (of the circadian cycle) thus obtained were in substantial agreement with other estimates for this or similar strains and showed no significant difference between LD 12:12 (wake 54.3%, NREM sleep 38.1%, REM sleep 7.6%) and DD (wake 53.1%, NREM sleep 39.9%, REM sleep 7.0%) conditions. All 10 mice exhibited clear circadian rhythms in each of the three states and wheel-running activity under both lighting conditions for the entire duration of observation. Probability functions, computed using stationary sections of data from all 10 mice, showed distinct waveforms for all three states and wheel running. These waveforms were remarkably similar under entrained and free-running conditions. This documentation of sustained circadian rhythmicity in sleep-wake state throughout observations of unprecedented length contradicts the currently common assertion that circadian control of sleep state is weaker than that of activity.


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.


2000 ◽  
Vol 279 (2) ◽  
pp. R586-R590 ◽  
Author(s):  
Marilyn J. Duncan ◽  
Anthony W. Deveraux

Aging involves many alterations in circadian rhythms, including a loss of sensitivity to both photic and nonphotic time signals. This study investigated the sensitivity of young and old hamsters to the phase advancing effect of a 6-h dark pulse on the locomotor activity rhythm. Each hamster was tested four times during a period of ∼9 mo; periods of exposure to a 14-h photoperiod were alternated with the periods of exposure to constant light (20–80 lx), during which the dark pulses were administered. There was no significant difference in the phase shifts exhibited by the young (4–10 mo) and old hamsters (19–25 mo) or in the amount of wheel running activity displayed during each dark pulse. However, young hamsters had a significantly greater propensity to exhibit split rhythms immediately after the dark pulses. These results suggest that, although aging does not reduce the sensitivity of the circadian pacemaker to this nonphotic signal, it alters one property of the pacemaker, i.e., the flexibility of the coupling of its component oscillators.


1997 ◽  
Vol 272 (4) ◽  
pp. R1219-R1225 ◽  
Author(s):  
K. Scarbrough ◽  
S. Losee-Olson ◽  
E. P. Wallen ◽  
F. W. Turek

Aging affects the regulation of diurnal and circadian rhythmicity. We tested the hypothesis that the age-related difference in the phase angle of entrainment of the locomotor activity rhythm to a light-dark (LD) cycle would be greater under LD 6:18 than LD 14:10. We also analyzed changes in quantitative aspects of wheel-running behavior according to age group. Young (9-wk-old), middle-aged (11- to 12-mo-old), and old (15- to 17-mo-old) male golden hamsters were entrained to a 14:10 LD cycle followed by re-entrainment to a 6:18 LD cycle. Fourteen days after the start of locomotor recording in LD 14:10 and again after 27 days in LD 6:18, the phase of activity onset, the total number of wheel revolutions performed per day, the peak intensity of wheel-running activity, the duration of the active period, and the level of fragmentation of locomotor activity were quantitated. We also studied the temporal distribution of the largest bout of wheel-running activity among the age groups in both photoperiods. Short days induced testicular regression at a similar rate among young, middle-aged, and old hamsters. The data are discussed in terms of the effects of age on overall circadian organization in the seasonally changing environment.


2011 ◽  
Vol 300 (3) ◽  
pp. R519-R530 ◽  
Author(s):  
Jens Hannibal ◽  
Hansen M. Hsiung ◽  
Jan Fahrenkrug

Neurons of the brain's biological clock located in the hypothalamic suprachiasmatic nucleus (SCN) generate circadian rhythms of physiology (core body temperature, hormone secretion, locomotor activity, sleep/wake, and heart rate) with distinct temporal phasing when entrained by the light/dark (LD) cycle. The neuropeptide vasoactive intestinal polypetide (VIP) and its receptor (VPAC2) are highly expressed in the SCN. Recent studies indicate that VIPergic signaling plays an essential role in the maintenance of ongoing circadian rhythmicity by synchronizing SCN cells and by maintaining rhythmicity within individual neurons. To further increase the understanding of the role of VPAC2 signaling in circadian regulation, we implanted telemetric devices and simultaneously measured core body temperature, spontaneous activity, and heart rate in a strain of VPAC2-deficient mice and compared these observations with observations made from mice examined by wheel-running activity. The study demonstrates that VPAC2 signaling is necessary for a functional circadian clock driving locomotor activity, core body temperature, and heart rate rhythmicity, since VPAC2-deficient mice lose the rhythms in all three parameters when placed under constant conditions (of either light or darkness). Furthermore, although 24-h rhythms for three parameters are retained in VPAC2-deficient mice during the LD cycle, the temperature rhythm displays markedly altered time course and profile, rising earlier and peaking ∼4–6 h prior to that of wild-type mice. The use of telemetric devices to measure circadian locomotor activity, temperature, and heart rate, together with the classical determination of circadian rhythms of wheel-running activity, raises questions about how representative wheel-running activity may be of other behavioral parameters, especially when animals have altered circadian phenotype.


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.


Genetics ◽  
1976 ◽  
Vol 83 (2) ◽  
pp. 393-407 ◽  
Author(s):  
Juan F Medrano ◽  
G A E Gall

ABSTRACT Food consumption, feed efficiency, metabolic rate and glucose utilization were studied throughout development in one control (1C) and three selected lines (3, 9, 10) of Tribolium castaneum that had been subjected to long term selection for 21-day pupae weight. Growth rate, body composition, cellular growth and the activity of four dehydrogenase enzymes in the same lines have been reported (Medrano and Gall 1976).—Larva of selected lines consumed 1.2 times as much food as the control and gained an average of 2.9 times as much weight. The rapid growth of the selected lines was associated with a gross feed efficiency 20 to 30% above that for the control line. There was also a small but consistent improvement in the conversion of digested food. Average digestibility was higher for selected lines.—There was little apparent differentiation between the control and selected lines in metabolic rate/individual, but the rate measured on a per-unit weight basis was two- to three-fold greater for the control during the active growth stages. Respiratory quotients (R.Q.) of 1.0, indicative of carbohydrate oxidation, were observed through larval growth in all lines. Pupae at 21 days showed R.Q. values greater than 1.0, which were interpreted as resulting from a phenomenon in insects in which CO2 is released by pupae, in large bursts at irregular intervals. The rate constant of glucose oxidation, measured as the rate of C14 labelled CO2 respired during 2- to 6-hour incubation periods, was two- to three-fold higher in the control. In addition, the control line larvae expired 5% to 17% more of the ingested C14 as CO2. It was apparent that control line individuals maintained a much more active turnover of metabolites but without an effective retention of carbon as body substances. The results are discussed in support of the hypothesis that selection for large body size resulted in improved control mechanisms that influence the biological efficiency of growth in Tribolium.


2001 ◽  
Vol 126 (2) ◽  
pp. 216-220 ◽  
Author(s):  
M.R. Foolad ◽  
G.Y. Lin

The genetic relationship between cold tolerance (CT) during seed germination and vegetative growth in tomato (Lycopersicon esculentum Mill.) was determined. An F2 population of a cross between accession PI120256 (cold tolerant during both seed germination and vegetative growth) and UCT5 (cold sensitive during both stages) was evaluated for germination under cold stress and the most cold tolerant progeny (the first 5% germinated) were selected. Selected progeny were grown to maturity and self-fertilized to produce F3 families (referred to as the selected F3 population). The selected F3 population was evaluated for CT separately during seed germination and vegetative growth and its performance was compared with that of a nonselected F3 population of the same cross. Results indicated that selection for CT during seed germination significantly improved CT of the progeny during germination; a realized heritability of 0.75 was obtained for CT during seed germination. However, selection for CT during germination did not affect plant CT during vegetative growth; there was no significant difference between the selected and nonselected F3 populations in either absolute CT [defined as shoot fresh weight (FW) under cold stress] or relative CT (defined as shoot FW under cold as a percentage of control). Results indicated that, in PI120256, CT during seed germination was genetically independent of CT during vegetative growth. Thus, to develop tomato cultivars with improved CT during different developmental stages, selection protocols that include all critical stages are necessary.


1988 ◽  
Vol 22 (1) ◽  
pp. 46-50 ◽  
Author(s):  
R. Pfeil

The effects of serial blood sampling on nocturnal locomotor activity, evasion, wheel-running activity and body mass were studied in male NMRI mice aged 7-8 weeks. The erythrocyte count, haematocrit and haemoglobin concentration at the beginning and end of the study showed no difference in group 1 (two samples per week, 0·08 ml each) while there was a significant decrease in the group 2 values (three samples per week, 0·08 ml each). The total amount of nocturnal locomotor activity decreased in the animals bled repeatedly while the periods with locomotor activity increased. These alterations appeared particularly after bleeding. In the test-group animals evasion showed a decrease compared with the untreated control animals, but there was no evidence of a relation to the timing of the bleedings.


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