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Compensatory elevation of voluntary activity in mouse mutants with impaired mitochondrial energy metabolism.

Lapointe J, G Hughes B, Bigras E, Hekimi S - Physiol Rep (2014)

Bottom Line: We find that both Mclk1(+/-) and RISP(+/P224S) males are capable of restoring their defective metabolic rates by making significantly more voluntary use of a running wheel compared to wild type.However, this increase in voluntary activity does not reflect their exercise capacity, which we found to be impaired as revealed by a shorter treadmill distance run before exhaustion.In contrast to what is observed in Mclk1(+/-) and RISP(+/P224S) mutants, Sod2(+/-) mice with elevated oxidative stress and major mitochondrial dysfunction did not increase voluntary activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, McGill University, Montréal, Quebec, Canada Agriculture and Agri-Food Canada, 2000 College St., Sherbrooke, J1M 0C8, Quebec, Canada.

No MeSH data available.


Related in: MedlinePlus

Increased voluntary activity and metabolic rate inRISP+/P224S males in presence of arunning wheel. Total number of wheel turns accomplished by 3‐ and 24‐month‐oldRISP+/+ andRISP+/P224S mice (n= 15–20) during the entire 48 h period: males (A) and females (B). Bars representmeans ± SEM and a value of P < 0.05 was considered significant.Voluntary activity on running wheel recorded at 2 h intervals throughout the 48 h period with a 12 hlight and 12 h dark cycle for both sexes at 3 months of age (C–D). Heat production was alsoassessed by indirect calorimetry for the entire experimental period (E–F). The shaded areasdemarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am. All pointsrepresent means ± SEM over 2 h intervals. A value of P < 0.05 for thegenotype effect was considered significant.
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fig06: Increased voluntary activity and metabolic rate inRISP+/P224S males in presence of arunning wheel. Total number of wheel turns accomplished by 3‐ and 24‐month‐oldRISP+/+ andRISP+/P224S mice (n= 15–20) during the entire 48 h period: males (A) and females (B). Bars representmeans ± SEM and a value of P < 0.05 was considered significant.Voluntary activity on running wheel recorded at 2 h intervals throughout the 48 h period with a 12 hlight and 12 h dark cycle for both sexes at 3 months of age (C–D). Heat production was alsoassessed by indirect calorimetry for the entire experimental period (E–F). The shaded areasdemarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am. All pointsrepresent means ± SEM over 2 h intervals. A value of P < 0.05 for thegenotype effect was considered significant.

Mentions: As in Mclk1+/− mice, mitochondrial electrontransport is impaired in RISP+/P224S miceand this leads to a significant decreased whole‐body metabolic rate for the males (Hughes andHekimi 2011). We sought to determine whether this also led toa change in spontaneous activity as in Mclk1+/−males. In addition, we scored the influence of age and sex on voluntary activity by using 3‐and 24‐month‐old males and females, which were all evaluated over a 48 h period. Weobserved that the RISP+/P224S males weresignificantly more active at both 3 and 24 months of age, but females were unaffected (Fig. 6A–D). Furthermore, the metabolic rate (heat production) ofthe RISP+/P224S males, which was found tobe lower than normal without running wheels (Hughes and Hekimi 2011), is restored to control values when they could use a running wheel (Fig. 6E). The level of heat production was not affected by theavailability of a running wheel in 3‐month‐oldRISP+/P224S females (Fig. 6F), consistent with their unchanged activity level relative towild‐type controls (Fig. 6F). We further observedthat the total number of wheel turns is higher forRISP+/+ than forMclk1+/+ 3‐month‐oldcontrols (Fig. 6A–B; compare to Figs. 2A, 3A), a difference thatis, likely the result of different genetic backgrounds, as has been previously documented (de Visseret al. 2007).


Compensatory elevation of voluntary activity in mouse mutants with impaired mitochondrial energy metabolism.

Lapointe J, G Hughes B, Bigras E, Hekimi S - Physiol Rep (2014)

Increased voluntary activity and metabolic rate inRISP+/P224S males in presence of arunning wheel. Total number of wheel turns accomplished by 3‐ and 24‐month‐oldRISP+/+ andRISP+/P224S mice (n= 15–20) during the entire 48 h period: males (A) and females (B). Bars representmeans ± SEM and a value of P < 0.05 was considered significant.Voluntary activity on running wheel recorded at 2 h intervals throughout the 48 h period with a 12 hlight and 12 h dark cycle for both sexes at 3 months of age (C–D). Heat production was alsoassessed by indirect calorimetry for the entire experimental period (E–F). The shaded areasdemarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am. All pointsrepresent means ± SEM over 2 h intervals. A value of P < 0.05 for thegenotype effect was considered significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255820&req=5

fig06: Increased voluntary activity and metabolic rate inRISP+/P224S males in presence of arunning wheel. Total number of wheel turns accomplished by 3‐ and 24‐month‐oldRISP+/+ andRISP+/P224S mice (n= 15–20) during the entire 48 h period: males (A) and females (B). Bars representmeans ± SEM and a value of P < 0.05 was considered significant.Voluntary activity on running wheel recorded at 2 h intervals throughout the 48 h period with a 12 hlight and 12 h dark cycle for both sexes at 3 months of age (C–D). Heat production was alsoassessed by indirect calorimetry for the entire experimental period (E–F). The shaded areasdemarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am. All pointsrepresent means ± SEM over 2 h intervals. A value of P < 0.05 for thegenotype effect was considered significant.
Mentions: As in Mclk1+/− mice, mitochondrial electrontransport is impaired in RISP+/P224S miceand this leads to a significant decreased whole‐body metabolic rate for the males (Hughes andHekimi 2011). We sought to determine whether this also led toa change in spontaneous activity as in Mclk1+/−males. In addition, we scored the influence of age and sex on voluntary activity by using 3‐and 24‐month‐old males and females, which were all evaluated over a 48 h period. Weobserved that the RISP+/P224S males weresignificantly more active at both 3 and 24 months of age, but females were unaffected (Fig. 6A–D). Furthermore, the metabolic rate (heat production) ofthe RISP+/P224S males, which was found tobe lower than normal without running wheels (Hughes and Hekimi 2011), is restored to control values when they could use a running wheel (Fig. 6E). The level of heat production was not affected by theavailability of a running wheel in 3‐month‐oldRISP+/P224S females (Fig. 6F), consistent with their unchanged activity level relative towild‐type controls (Fig. 6F). We further observedthat the total number of wheel turns is higher forRISP+/+ than forMclk1+/+ 3‐month‐oldcontrols (Fig. 6A–B; compare to Figs. 2A, 3A), a difference thatis, likely the result of different genetic backgrounds, as has been previously documented (de Visseret al. 2007).

Bottom Line: We find that both Mclk1(+/-) and RISP(+/P224S) males are capable of restoring their defective metabolic rates by making significantly more voluntary use of a running wheel compared to wild type.However, this increase in voluntary activity does not reflect their exercise capacity, which we found to be impaired as revealed by a shorter treadmill distance run before exhaustion.In contrast to what is observed in Mclk1(+/-) and RISP(+/P224S) mutants, Sod2(+/-) mice with elevated oxidative stress and major mitochondrial dysfunction did not increase voluntary activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, McGill University, Montréal, Quebec, Canada Agriculture and Agri-Food Canada, 2000 College St., Sherbrooke, J1M 0C8, Quebec, Canada.

No MeSH data available.


Related in: MedlinePlus