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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

Voluntary activity in 15‐month‐oldMclk1+/−,Sod2+/−, andMclk1+/−Sod2+/− mutants. Assessment of whole‐bodymetabolic rate and voluntary activity in 15‐month‐old wild‐type,Mclk1+/−,Sod2+/−, andSod2+/−Mclk1+/−males on the DBA/2J/B6 F1background. Total number of wheel turns accomplished during a 60 h period (A). Bars represent means± SEM. Bars with different letters (a, b) differ from each other while bars with a letter incommon are not statistically different (P < 0.05). Continuous recording ofvoluntary activity on running wheel through a 60 h period with a 12 h light and 12 h dark cycle.(B). Metabolic rate parameters were also assessed by indirect calorimetry for the entireexperimental period. The shaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time“0” is 7:00 am. Changes in oxygen consumption (C), respiratory exchange ratio (D) andheat production (E). All points represent means ± SEM over 2 h intervals. A value ofP < 0.05 for the genotype effect was considered significant.
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fig04: Voluntary activity in 15‐month‐oldMclk1+/−,Sod2+/−, andMclk1+/−Sod2+/− mutants. Assessment of whole‐bodymetabolic rate and voluntary activity in 15‐month‐old wild‐type,Mclk1+/−,Sod2+/−, andSod2+/−Mclk1+/−males on the DBA/2J/B6 F1background. Total number of wheel turns accomplished during a 60 h period (A). Bars represent means± SEM. Bars with different letters (a, b) differ from each other while bars with a letter incommon are not statistically different (P < 0.05). Continuous recording ofvoluntary activity on running wheel through a 60 h period with a 12 h light and 12 h dark cycle.(B). Metabolic rate parameters were also assessed by indirect calorimetry for the entireexperimental period. The shaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time“0” is 7:00 am. Changes in oxygen consumption (C), respiratory exchange ratio (D) andheat production (E). All points represent means ± SEM over 2 h intervals. A value ofP < 0.05 for the genotype effect was considered significant.

Mentions: Sod2+/− mice sustain mitochondrial oxidativestress that affects their metabolic rate and exercise capacity (Williams et al. 1998; Kinugawa 2005). Wehave previously shown that at 15 months of age these features are dramatically alleviated in doubleheterozygous Sod2+/−Mclk1+/− animals (Lapointe et al. 2009). The metabolic rate of such 15‐month‐old malemice of similar body weight was first analyzed without access to running wheels and no significantdifferences between genotypes were observed for VO2, RER or heat production (data notshown). This contrasts with our findings with 3‐month‐oldMclk1+/− males. However, we have previously shownthat most phenotypes of Mclk1+/− mice evolve towardcontrol values with aging (Lapointe et al. 2009). The15‐month‐old male mice were then subjected to voluntary activity analysis for a 60 hperiod by allowing them continuous access to a running wheel. As expected, based on previousresearch, Sod2+/− animals were not very active,although the difference with the wild‐type controls did not reach significance (Fig. 4A). However, the total number of wheel turns accumulated by thedouble heterozygotes was about fivefold greater than that recorded forSod2+/− mutants (Fig. 4A). This difference between the genotypes tended to be consistently apparentthroughout the 60 h period (Fig. 4B). Analysis of theVO2, RER and heat production did not reveal any effect of genotype throughout theexperimental period (Fig. 4C–E).


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)

Voluntary activity in 15‐month‐oldMclk1+/−,Sod2+/−, andMclk1+/−Sod2+/− mutants. Assessment of whole‐bodymetabolic rate and voluntary activity in 15‐month‐old wild‐type,Mclk1+/−,Sod2+/−, andSod2+/−Mclk1+/−males on the DBA/2J/B6 F1background. Total number of wheel turns accomplished during a 60 h period (A). Bars represent means± SEM. Bars with different letters (a, b) differ from each other while bars with a letter incommon are not statistically different (P < 0.05). Continuous recording ofvoluntary activity on running wheel through a 60 h period with a 12 h light and 12 h dark cycle.(B). Metabolic rate parameters were also assessed by indirect calorimetry for the entireexperimental period. The shaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time“0” is 7:00 am. Changes in oxygen consumption (C), respiratory exchange ratio (D) andheat production (E). All points represent means ± SEM over 2 h intervals. A value ofP < 0.05 for the genotype effect was considered significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig04: Voluntary activity in 15‐month‐oldMclk1+/−,Sod2+/−, andMclk1+/−Sod2+/− mutants. Assessment of whole‐bodymetabolic rate and voluntary activity in 15‐month‐old wild‐type,Mclk1+/−,Sod2+/−, andSod2+/−Mclk1+/−males on the DBA/2J/B6 F1background. Total number of wheel turns accomplished during a 60 h period (A). Bars represent means± SEM. Bars with different letters (a, b) differ from each other while bars with a letter incommon are not statistically different (P < 0.05). Continuous recording ofvoluntary activity on running wheel through a 60 h period with a 12 h light and 12 h dark cycle.(B). Metabolic rate parameters were also assessed by indirect calorimetry for the entireexperimental period. The shaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time“0” is 7:00 am. Changes in oxygen consumption (C), respiratory exchange ratio (D) andheat production (E). All points represent means ± SEM over 2 h intervals. A value ofP < 0.05 for the genotype effect was considered significant.
Mentions: Sod2+/− mice sustain mitochondrial oxidativestress that affects their metabolic rate and exercise capacity (Williams et al. 1998; Kinugawa 2005). Wehave previously shown that at 15 months of age these features are dramatically alleviated in doubleheterozygous Sod2+/−Mclk1+/− animals (Lapointe et al. 2009). The metabolic rate of such 15‐month‐old malemice of similar body weight was first analyzed without access to running wheels and no significantdifferences between genotypes were observed for VO2, RER or heat production (data notshown). This contrasts with our findings with 3‐month‐oldMclk1+/− males. However, we have previously shownthat most phenotypes of Mclk1+/− mice evolve towardcontrol values with aging (Lapointe et al. 2009). The15‐month‐old male mice were then subjected to voluntary activity analysis for a 60 hperiod by allowing them continuous access to a running wheel. As expected, based on previousresearch, Sod2+/− animals were not very active,although the difference with the wild‐type controls did not reach significance (Fig. 4A). However, the total number of wheel turns accumulated by thedouble heterozygotes was about fivefold greater than that recorded forSod2+/− mutants (Fig. 4A). This difference between the genotypes tended to be consistently apparentthroughout the 60 h period (Fig. 4B). Analysis of theVO2, RER and heat production did not reveal any effect of genotype throughout theexperimental period (Fig. 4C–E).

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