Limits...
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

Sex‐specific decreased in whole‐body metabolism inMclk1+/− mice. Resting metabolic parameters werecontinuously assessed by indirect calorimetry performed over a 24 h period with a 12 h light and 12h dark cycle in 3‐month‐old Mclk1+/+and Mclk1+/− mice (n =10–12). Significant changes in oxygen consumption rate (A) and heat production (C) wereobserved between genotypes for males. In contrast, oxygen consumption (B), heat production, (D) andrespiratory exchange ratio (E,F) were similar betweenMclk1+/+ andMclk1+/− females throughout the 24 h period. Theshaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am.All points represent means ± SEM averaged over 2 h intervals. A value of P< 0.05 for the genotype effect was considered significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4255820&req=5

fig01: Sex‐specific decreased in whole‐body metabolism inMclk1+/− mice. Resting metabolic parameters werecontinuously assessed by indirect calorimetry performed over a 24 h period with a 12 h light and 12h dark cycle in 3‐month‐old Mclk1+/+and Mclk1+/− mice (n =10–12). Significant changes in oxygen consumption rate (A) and heat production (C) wereobserved between genotypes for males. In contrast, oxygen consumption (B), heat production, (D) andrespiratory exchange ratio (E,F) were similar betweenMclk1+/+ andMclk1+/− females throughout the 24 h period. Theshaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am.All points represent means ± SEM averaged over 2 h intervals. A value of P< 0.05 for the genotype effect was considered significant.

Mentions: All mice were weighed prior to the experiments and no differences were observed betweenheterozygotes and controls (data not shown). We have previously reported that there is also nodifferences in body composition (Liu et al. 2005; Lapointeand Hekimi 2008). Similarly, an evaluation of both bodyweight and food intake at 3, 12, and 23 months of age did not show significant differences betweengenotypes, with the exception of 23‐month‐oldMclk1+/− females that were found to be slightlyheavier than their wild‐type siblings (data not shown). Whole‐body metabolicparameters were assessed by indirect calorimetry in 3‐month‐old male and femaleMclk1+/− mice in the Balb/c geneticbackground (Fig. 1). Analysis of oxygen consumption(VO2) showed the expected diurnal pattern characterized by an increased VO2during the dark period, when mice are more active, compared to the light period (Fig. 1A and B). Throughout the 24 h period, theMclk1+/− male mice showed decreased VO2compared to controls whereas the slight reduction observed forMclk1+/− females did not reach significance (Fig.1A and B). Similar results were obtained for heatproduction, which is a calculated measure of metabolic rate. We observed the predicted diurnalrhythm with increased heat production during the night and found that, in contrast to the females,the Mclk1+/− males produced less heat than controls(Fig. 1C and D). We also measured the respiratory exchangeratio (RER) which correspond to the volume of carbon dioxide produced over a given time(VCO2) divided by the oxygen that was simultaneously consumed (RER =VCO2/VO2) and indicates which substrates are preferably oxidized. Aratio near 1 indicates lipid oxidation, while a value of 0.7 is an indication of carbohydrateoxidation. We observed a trend toward fat oxidation as the experimental period progressed from dayto night and no statistically significant differences in RER ratio could be observed betweenMclk1+/+ andMclk1+/− mice for both sexes (Fig. 1E and F).


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)

Sex‐specific decreased in whole‐body metabolism inMclk1+/− mice. Resting metabolic parameters werecontinuously assessed by indirect calorimetry performed over a 24 h period with a 12 h light and 12h dark cycle in 3‐month‐old Mclk1+/+and Mclk1+/− mice (n =10–12). Significant changes in oxygen consumption rate (A) and heat production (C) wereobserved between genotypes for males. In contrast, oxygen consumption (B), heat production, (D) andrespiratory exchange ratio (E,F) were similar betweenMclk1+/+ andMclk1+/− females throughout the 24 h period. Theshaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am.All points represent means ± SEM averaged over 2 h intervals. A value of P< 0.05 for the genotype effect was considered significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Sex‐specific decreased in whole‐body metabolism inMclk1+/− mice. Resting metabolic parameters werecontinuously assessed by indirect calorimetry performed over a 24 h period with a 12 h light and 12h dark cycle in 3‐month‐old Mclk1+/+and Mclk1+/− mice (n =10–12). Significant changes in oxygen consumption rate (A) and heat production (C) wereobserved between genotypes for males. In contrast, oxygen consumption (B), heat production, (D) andrespiratory exchange ratio (E,F) were similar betweenMclk1+/+ andMclk1+/− females throughout the 24 h period. Theshaded areas demarcate the dark phases (from 7:00 pm to 7:00 am). Time “0” is 7:00 am.All points represent means ± SEM averaged over 2 h intervals. A value of P< 0.05 for the genotype effect was considered significant.
Mentions: All mice were weighed prior to the experiments and no differences were observed betweenheterozygotes and controls (data not shown). We have previously reported that there is also nodifferences in body composition (Liu et al. 2005; Lapointeand Hekimi 2008). Similarly, an evaluation of both bodyweight and food intake at 3, 12, and 23 months of age did not show significant differences betweengenotypes, with the exception of 23‐month‐oldMclk1+/− females that were found to be slightlyheavier than their wild‐type siblings (data not shown). Whole‐body metabolicparameters were assessed by indirect calorimetry in 3‐month‐old male and femaleMclk1+/− mice in the Balb/c geneticbackground (Fig. 1). Analysis of oxygen consumption(VO2) showed the expected diurnal pattern characterized by an increased VO2during the dark period, when mice are more active, compared to the light period (Fig. 1A and B). Throughout the 24 h period, theMclk1+/− male mice showed decreased VO2compared to controls whereas the slight reduction observed forMclk1+/− females did not reach significance (Fig.1A and B). Similar results were obtained for heatproduction, which is a calculated measure of metabolic rate. We observed the predicted diurnalrhythm with increased heat production during the night and found that, in contrast to the females,the Mclk1+/− males produced less heat than controls(Fig. 1C and D). We also measured the respiratory exchangeratio (RER) which correspond to the volume of carbon dioxide produced over a given time(VCO2) divided by the oxygen that was simultaneously consumed (RER =VCO2/VO2) and indicates which substrates are preferably oxidized. Aratio near 1 indicates lipid oxidation, while a value of 0.7 is an indication of carbohydrateoxidation. We observed a trend toward fat oxidation as the experimental period progressed from dayto night and no statistically significant differences in RER ratio could be observed betweenMclk1+/+ andMclk1+/− mice for both sexes (Fig. 1E and F).

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