scholarly journals Obesogenic diet and targeted deletion of potassium channel Kv1.3 have differing effects on voluntary exercise in mice

2019 ◽  
Author(s):  
Brandon M. Chelette ◽  
Abigail Thomas ◽  
Debra Ann Fadool
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Dark Phase ◽  
List Type ◽  
Running Wheel ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Obesogenic Diet

ABSTRACTVoluntary exercise is frequently employed as an intervention for obesity. The voltage-gated potassium Kv1.3 is also receiving attention as a therapeutic target for obesity, in addition to potential therapeutic capabilities for neuroinflammatory diseases. To investigate combinatorial effects of these two therapies, we have compared the metabolic status and voluntary exercise behavior of both wildtype mice and a transgenic line of mice that are genetic knockouts for Kv1.3 when provided with a running wheel and maintained on diets of differing fat content and caloric density. We tracked metabolic parameters and wheel running behavior while maintaining the mice on their assigned treatment for 6 months. Wildtype mice maintained on the fatty diet gain a significant amount of bodyweight and adipose tissue and display significantly impaired glucose tolerance, though all these effects were partially reduced with provision of a running wheel. Similarly to previous studies, the Kv1.3-null mice were resistant to obesity, increased adiposity, and impaired glucose tolerance. Both wildtype and Kv1.3-null mice maintained on the fatty diet displayed increased wheel running activity compared to CF-fed mice which was caused primarily by a significant increase in amount of time spent running as opposed to an increase in running velocity. Interestingly, the patterns of running behavior differ between wildtype and Kv1.3-null mice, especially in how their resting periods are distributed through the dark phase. These studies indicate that voluntary exercise combats metabolic maladies and running behavior is modified by both consumption of an obesogenic diet and deletion of the Kv1.3 channel.NEW and NOTEWORTHYKv1.3-null mice exhibit different running and resting patterns compared to wildtype miceMice maintained on an obesogenic diet (32% kcal from fat) exhibit increased running distance and increased time spent running compared to mice fed normal rodent chow.

Activity rhythm of golden hamster (Mesocricetus auratus) can be entrained to a 19-h light-dark cycle

2005 ◽  
Vol 289 (4) ◽  
pp. R998-R1005 ◽  
Author(s):  
Juan J. Chiesa ◽  
Montserrat Anglès-Pujolràs ◽  
Antoni Díez-Noguera ◽  
Trinitat Cambras
Keyword(s):  
Golden Hamster ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Mesocricetus Auratus ◽  
Precise Determination ◽  
Dark Cycle ◽  
Running Wheel ◽  
Running Activity ◽  
Wheel Running Activity

Both temporary access to a running wheel and temporary exposure to light systematically influence the phase producing entrainment of the circadian activity rhythm in the golden hamster ( Mesocricetus auratus). However, precise determination of entrainment limits remains methodologically difficult, because such calculations may be influenced by varying experimental paradigms. In this study, effects on the entrainment of the activity pattern during successive light-dark (LD) cycles of stepwise decreasing periods, as well as wheel running activity, were investigated. In particular, the hamster activity rhythm under LD cycles with a period (T) shorter than 22 h was studied, i.e., when the LD cycle itself had been shown to be an insufficiently strong zeitgeber to synchronize activity rhythms. Indeed, it was confirmed that animals without a wheel do not entrain under 11:11-h LD cycles (T = 22 h). Subsequently providing hamsters continuous access to a running wheel established entrainment to T = 22 h. Moreover, this paradigm underwent further reductions of the T period to T = 19.6 h without loss of entrainment. Furthermore, restricting access to the wheel did not result in loss of entrainment, while even entrainment to T = 19 h was observed. To explain this observed shift in the lower entrainment limit, our speculation centers on changes in pacemaker response facilitated by stepwise changes of T spaced very far apart, thus allowing time for adaptation.

Genetic influence on daily wheel running activity level

2004 ◽  
Vol 19 (3) ◽  
pp. 270-276 ◽  
Author(s):  
J. Timothy Lightfoot ◽  
Michael J. Turner ◽  
Meredith Daves ◽  
Anna Vordermark ◽  
Steven R. Kleeberger
Keyword(s):  
Wheel Running ◽  
Activity Level ◽  
Male Mice ◽  
Running Wheel ◽  
Female Mice ◽  
Running Activity ◽  
Daily Exercise ◽  
Wheel Running Activity ◽  
Wheel Activity ◽  
Daily Distance

This project was designed to determine the genetic (between-strain) and environmental (within-strain) variance in daily running wheel activity level in inbred mice. Five male and five female mice, 9.7–15.3 wk old, from each of 13 strains (A/J, AKR/J, BALB/cJ, C3H/HeJ, C57Bl/6J, C57L/J, C3Heb/FeJ, CBA/J, DBA/2J, SWR/J, MRL/MpJ, SPRET/Ei, and CAST/Ei) as well as five female NZB/BinJ mice were housed individually. A running wheel in each cage was interfaced with a magnetic sensor to measure total daily distance and exercise time for each animal every 24 h for 21 consecutive days (3 wk). Average daily distance (km), duration (min), and velocity (m/min) for each strain was then calculated. Significant interstrain differences in average daily distance ( P < 0.001), average daily exercise duration ( P < 0.0001), and average daily exercise velocity ( P < 0.0001) were found, with C57L/J mice running farther and faster than the other strains. Sex was a significant factor in daily running wheel activity, with female mice running an average of 20% farther ( P = 0.01) and 38% faster ( P < 0.0001) than male mice. The male mice ran 15% longer duration on a daily basis ( P = 0.0091). Weight was only associated with exercise velocity in the female mice, but this relationship was not significant when subdivided by strain. Broad-sense heritability estimates on the physical activity differed by sex (for distance, male 31–48% and female 12–22%; for duration, male 44–61% and female 12–21%; for velocity, male 49–66% and female 44–61%). In conclusion, these data indicate that daily running wheel activity level in mice is significantly affected by genetic background and sex.

Altered sleep and behavioral activity phenotypes in PER3-deficient mice

2011 ◽  
Vol 301 (6) ◽  
pp. R1821-R1830 ◽  
Author(s):  
Sibah Hasan ◽  
Daan R. van der Veen ◽  
Raphaelle Winsky-Sommerer ◽  
Derk-Jan Dijk ◽  
Simon N. Archer
Keyword(s):  
Rem Sleep ◽  
Wheel Running ◽  
Nrem Sleep ◽  
Light Period ◽  
Behavioral Activity ◽  
Dark Phase ◽  
Running Activity ◽  
Sleep Homeostasis ◽  
Wheel Running Activity ◽  
Delta Activity

Sleep homeostasis and circadian rhythmicity interact to determine the timing of behavioral activity. Circadian clock genes contribute to circadian rhythmicity centrally and in the periphery, but some also have roles within sleep regulation. The clock gene Period3 ( Per3) has a redundant function within the circadian system and is associated with sleep homeostasis in humans. This study investigated the role of PER3 in sleep/wake activity and sleep homeostasis in mice by recording wheel-running activity under baseline conditions in wild-type (WT; n = 54) and in PER3-deficient ( Per3−/−; n = 53) mice, as well as EEG-assessed sleep before and after 6 h of sleep deprivation in WT ( n = 7) and Per3−/− ( n = 8) mice. Whereas total activity and vigilance states did not differ between the genotypes, the temporal distribution of wheel-running activity, vigilance states, and EEG delta activity was affected by genotype. In Per3−/− mice, running wheel activity was increased, and REM sleep and NREM sleep were reduced in the middle of the dark phase, and delta activity was enhanced at the end of the dark phase. At the beginning of the baseline light period, there was less wakefulness and more REM and NREM sleep in Per3−/− mice. Per3−/− mice spent less time in wakefulness and more time in NREM sleep in the light period immediately after sleep deprivation, and REM sleep accumulated more slowly during the recovery dark phase. These data confirm a role for PER3 in sleep-wake timing and sleep homeostasis.

scholarly journals Voluntary exercise is motivated by ghrelin, possibly related to the central reward circuit

2020 ◽  
Vol 244 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Hiroharu Mifune ◽  
Yuji Tajiri ◽  
Yusuke Sakai ◽  
Yukie Kawahara ◽  
Kento Hara ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Ghrelin Concentration ◽  
Ghrelin Receptor ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Ghrelin Receptor Agonist ◽  
Plasma Ghrelin Concentration ◽  
Reward Circuit

We previously reported that voluntary exercise contributed to the amelioration of abnormal feeding behavior with a concomitant restoration of ghrelin production in a rat model of obesity, suggesting a possible relationship between exercise and appetite-regulating hormones. Ghrelin is known to be involved in the brain reward circuits via dopamine neurons related to motivational properties. We investigated the relevance of ghrelin as an initiator of voluntary exercise as well as feeding behavior. The plasma ghrelin concentration fluctuates throughout the day with its peak at the beginning of the dark period in the wild-type (WT) mice with voluntary exercise. Although predominant increases in wheel running activity were observed accordant to the peak of plasma ghrelin concentration in the WT mice, those were severely attenuated in the ghrelin-knockout (GKO) mice under either ad libitum or time-restricted feeding. A single injection of ghrelin receptor agonist brought about and reproduced a marked enhancement of wheel running activity, in contrast to no effect by the continuous administration of the same drug. Brain dopamine levels (DAs) were enhanced after food consumption in the WT mice under voluntary exercise. Although the acceleration of DAs were apparently blunted in the GKO mice, they were dramatically revived after the administration of ghrelin receptor agonist, suggesting the relevance of ghrelin in the reward circuit under voluntary exercise. These findings emphasize that the surge of ghrelin plays a crucial role in the formation of motivation for the initiation of voluntary exercise possibly related to the central dopamine system.

Fermented soymilk increases voluntary wheel running activity and sexual behavior in male rats

2010 ◽  
Vol 35 (6) ◽  
pp. 749-754 ◽  
Author(s):  
Takuya Sato ◽  
Yasutomo Shinohara ◽  
Daisuke Kaneko ◽  
Ikuko Nishimura ◽  
Asahi Matsuyama
Keyword(s):  
Sexual Behavior ◽  
Wheel Running ◽  
Normal Diet ◽  
Voluntary Exercise ◽  
Male Rats ◽  
Voluntary Wheel Running ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Leuconostoc Pseudomesenteroides ◽  
Voluntary Wheel

Wheel running by rodents is thought to reflect voluntary exercise in humans. The present study examined the effect of fermented soymilk (FSM) on voluntary wheel running in rats. FSM was prepared from soymilk (SM) using the bacteria Leuconostoc pseudomesenteroides . The rats were fed a normal diet for 3 weeks followed by a 3-week administration of diet containing FSM or SM (5% w/w), and then the diets were switched back to a normal diet for 3 weeks. The voluntary wheel running activity was increased by FSM administration, although no changes were observed by SM administration. This effect was observed 2 weeks after FSM administration and lasted 1 week after deprivation of FSM. Then we evaluated the effect of FSM on sexual behavior in male rats. FSM administration for 10 days significantly increased the number of mounts. The protein expression of tyrosine hydroxylase (TH) increased in the hippocampus by FSM administration and it is suggested that FSM may change norepinephrine or dopamine signaling in the brain. Our study provides the first evidence that FSM increases voluntary wheel running activity and sexual behavior and suggests that TH may be involved in these effects.

Differential effects of food restriction on pituitary-testicular function in mice

1985 ◽  
Vol 248 (2) ◽  
pp. R181-R189 ◽  
Author(s):  
J. L. Blank ◽  
C. Desjardins
Keyword(s):  
Food Intake ◽  
Animal Models ◽  
Food Restriction ◽  
Wheel Running ◽  
Temporal Organization ◽  
Deer Mice ◽  
House Mice ◽  
Testicular Function ◽  
Running Activity ◽  
Wheel Running Activity

The reproductive responses of two species of wild rodents, house mice and deer mice, were evaluated following a 30% reduction in food intake for 5 wk. These animal models were chosen as prototypes of other rodent species because each employs unique functional adjustments when confronted with reduced resources in their natural habitats. Modest inanition failed to alter pituitary-testicular function in house mice; neither spermatogenesis nor plasma concentrations of luteinizing hormone (LH) and testosterone were modified. In sharp distinction, deer mice exposed to restricted food intake showed significant reductions in plasma LH and testosterone and an accompanying loss in spermatogenesis. Reduced food intake also caused pronounced shifts in the temporal organization and amount of wheel-running activity in both animal models, albeit in a dichotomous fashion. House mice exhibited the same amount of wheel-running activity throughout inanition, but the diel periodicity of locomotor behavior was shifted from the dark to the light period. Deer mice, in comparison, significantly curtailed wheel-running activity during the dark hours but ran in precise phase relationship with the light-dark cycle. Taken together, our results establish that the male reproductive system and its supporting neuroendocrine and behavioral correlates can be disrupted by modest levels of food restriction in certain animal models.

Genetic analysis of daily physical activity using a mouse chromosome substitution strain

2009 ◽  
Vol 39 (1) ◽  
pp. 47-55 ◽  
Author(s):  
He S. Yang ◽  
Martha H. Vitaterna ◽  
Aaron D. Laposky ◽  
Kazuhiro Shimomura ◽  
Fred W. Turek
Keyword(s):  
Physical Activity ◽  
Physical Activity Level ◽  
Wheel Running ◽  
Daily Physical Activity ◽  
Activity Level ◽  
Constant Darkness ◽  
Circadian Period ◽  
Chromosome 13 ◽  
Running Activity ◽  
Wheel Running Activity

There is considerable evidence for a genetic basis underlying individual differences in spontaneous physical activity in humans and animals. Previous publications indicate that the physical activity level and pattern vary among inbred strains of mice and identified a genomic region on chromosome 13 as quantitative trait loci (QTL) for physical activity. To confirm and further characterize the role of chromosome 13 in regulating daily physical activity level and pattern, we conducted a comprehensive phenotypic study in the chromosome 13 substitution strain (CSS-13) in which the individual chromosome 13 from the A/J strain was substituted into an otherwise complete C57BL/6J (B6) genome. The B6 and A/J parental strains exhibited pronounced differences in daily physical activity, sleep-wake structure, circadian period and body weight. Here we report that a single A/J chromosome 13 in the context of a B6 genetic background conferred a profound reduction in both total cage activity and wheel-running activity under a 14:10-h light-dark cycle, as well as in constant darkness, compared with B6 controls. Additionally, CSS-13 mice differed from B6 controls in the diurnal distribution of activity and the day-to-day variability in activity onset. We further performed a linkage analysis and mapped a significant QTL on chromosome 13 regulating the daily wheel running activity level in mice. Taken together, our findings indicate a QTL on chromosome 13 with dramatic and specific effects on daily voluntary physical activity, but not on circadian period, sleep, or other aspects of activity that are different between B6 and A/J strains.

scholarly journals Strain screen and haplotype association mapping of wheel running in inbred mouse strains

2010 ◽  
Vol 109 (3) ◽  
pp. 623-634 ◽  
Author(s):  
J. Timothy Lightfoot ◽  
Larry Leamy ◽  
Daniel Pomp ◽  
Michael J. Turner ◽  
Anthony A. Fodor ◽  
...  
Keyword(s):  
Physical Activity ◽  
Association Mapping ◽  
Wheel Running ◽  
Association Studies ◽  
Mouse Strains ◽  
Haplotype Association ◽  
Male And Female ◽  
Female Mice ◽  
Running Activity ◽  
Wheel Running Activity

Previous genetic association studies of physical activity, in both animal and human models, have been limited in number of subjects and genetically homozygous strains used as well as number of genomic markers available for analysis. Expansion of the available mouse physical activity strain screens and the recently published dense single-nucleotide polymorphism (SNP) map of the mouse genome (≈8.3 million SNPs) and associated statistical methods allowed us to construct a more generalizable map of the quantitative trait loci (QTL) associated with physical activity. Specifically, we measured wheel running activity in male and female mice (average age 9 wk) in 41 inbred strains and used activity data from 38 of these strains in a haplotype association mapping analysis to determine QTL associated with activity. As seen previously, there was a large range of activity patterns among the strains, with the highest and lowest strains differing significantly in daily distance run (27.4-fold), duration of activity (23.6-fold), and speed (2.9-fold). On a daily basis, female mice ran further (24%), longer (13%), and faster (11%). Twelve QTL were identified, with three (on Chr. 12, 18, and 19) in both male and female mice, five specific to males, and four specific to females. Eight of the 12 QTL, including the 3 general QTL found for both sexes, fell into intergenic areas. The results of this study further support the findings of a moderate to high heritability of physical activity and add general genomic areas applicable to a large number of mouse strains that can be further mined for candidate genes associated with regulation of physical activity. Additionally, results suggest that potential genetic mechanisms arising from traditional noncoding regions of the genome may be involved in regulation of physical activity.

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