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PGC-1α is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle.

Rowe GC, El-Khoury R, Patten IS, Rustin P, Arany Z - PLoS ONE (2012)

Bottom Line: The transcriptional coactivator PGC-1α, a potent regulator of metabolism in numerous tissues, is widely believed to be required for EIMB.We show here that this is not the case.Induction of metabolic genes after 2 weeks of in-cage voluntary wheel running was intact.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
Exercise confers numerous health benefits, many of which are thought to stem from exercise-induced mitochondrial biogenesis (EIMB) in skeletal muscle. The transcriptional coactivator PGC-1α, a potent regulator of metabolism in numerous tissues, is widely believed to be required for EIMB. We show here that this is not the case. Mice engineered to lack PGC-1α specifically in skeletal muscle (Myo-PGC-1αKO mice) retained intact EIMB. The exercise capacity of these mice was comparable to littermate controls. Induction of metabolic genes after 2 weeks of in-cage voluntary wheel running was intact. Electron microscopy revealed no gross abnormalities in mitochondria, and the mitochondrial biogenic response to endurance exercise was as robust in Myo-PGC-1αKO mice as in wildtype mice. The induction of enzymatic activity of the electron transport chain by exercise was likewise unperturbed in Myo-PGC-1αKO mice. These data demonstrate that PGC-1α is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle, in sharp contrast to the prevalent assumption in the field.

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Mild decrease voluntary-wheel performance in Myo-PGC-1α animals.A.) 10 to 12 week old Myo-PGC-1αKO mice and control littermates were individually housed in voluntary running wheel cages with electronic monitoring system for 2 weeks. Tracing of wheel activity, in revolutions per minute is shown. B.) Average number of revolutions per minute C.)Total distance ran in kilometers (km). Error bars indicate s.e.m.; n >6 per group in all panels. * - P<0.05 compared to control.
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pone-0041817-g001: Mild decrease voluntary-wheel performance in Myo-PGC-1α animals.A.) 10 to 12 week old Myo-PGC-1αKO mice and control littermates were individually housed in voluntary running wheel cages with electronic monitoring system for 2 weeks. Tracing of wheel activity, in revolutions per minute is shown. B.) Average number of revolutions per minute C.)Total distance ran in kilometers (km). Error bars indicate s.e.m.; n >6 per group in all panels. * - P<0.05 compared to control.

Mentions: Mice lacking PGC-1α throughout the body have numerous systemic effects, including hypermetabolism, hyperactivity, and a reluctance to exercise [35], [51], rendering them a poor model to study EIMB in skeletal muscle. Mice bearing myocyte-specific deletion of PGC-1α (Myo-PGC-1αKO mice) were thus used. The mice were generated by Cre/Lox recombination and transgenic expression of Cre with a myogenin/MEF2 promoter/enhancer construct, as previously described [35], [52], [53]. 12-week old female Myo-PGC-1αKO mice and littermate control mice were allowed to exercise in individually housed cages with hanging voluntary running wheels for 12 days. The wheel revolutions per minute were assessed over the time course using an in-cage monitoring system (Figure 1A). As shown in Figure 1, both Myo-PGC-1αKO and control mice voluntarily ran nightly, and rested daily, running approximately 10 hours/day for an approximate calculated total distance of 100 km over the 2-week period. Mice of both genotypes initially ran at 20–40 revolutions/minute, and increased their running performance over the subsequent 9 days to a plateau of approximately 60–80 revolutions/minute. Overall, the Myo-PGC-1αKO mice revealed a mild, non-statistically significant, reduction in exercise performance, as assessed by both the average revolutions per min (Figure 1B) and total distance run (Figure 1C). Therefore the Myo-PGC-1αKO mice provide a good system for assessing the effects of deleting PGC-1α in skeletal muscle without any of the negative effects of germline deletion of PGC-1α.


PGC-1α is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle.

Rowe GC, El-Khoury R, Patten IS, Rustin P, Arany Z - PLoS ONE (2012)

Mild decrease voluntary-wheel performance in Myo-PGC-1α animals.A.) 10 to 12 week old Myo-PGC-1αKO mice and control littermates were individually housed in voluntary running wheel cages with electronic monitoring system for 2 weeks. Tracing of wheel activity, in revolutions per minute is shown. B.) Average number of revolutions per minute C.)Total distance ran in kilometers (km). Error bars indicate s.e.m.; n >6 per group in all panels. * - P<0.05 compared to control.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3404101&req=5

pone-0041817-g001: Mild decrease voluntary-wheel performance in Myo-PGC-1α animals.A.) 10 to 12 week old Myo-PGC-1αKO mice and control littermates were individually housed in voluntary running wheel cages with electronic monitoring system for 2 weeks. Tracing of wheel activity, in revolutions per minute is shown. B.) Average number of revolutions per minute C.)Total distance ran in kilometers (km). Error bars indicate s.e.m.; n >6 per group in all panels. * - P<0.05 compared to control.
Mentions: Mice lacking PGC-1α throughout the body have numerous systemic effects, including hypermetabolism, hyperactivity, and a reluctance to exercise [35], [51], rendering them a poor model to study EIMB in skeletal muscle. Mice bearing myocyte-specific deletion of PGC-1α (Myo-PGC-1αKO mice) were thus used. The mice were generated by Cre/Lox recombination and transgenic expression of Cre with a myogenin/MEF2 promoter/enhancer construct, as previously described [35], [52], [53]. 12-week old female Myo-PGC-1αKO mice and littermate control mice were allowed to exercise in individually housed cages with hanging voluntary running wheels for 12 days. The wheel revolutions per minute were assessed over the time course using an in-cage monitoring system (Figure 1A). As shown in Figure 1, both Myo-PGC-1αKO and control mice voluntarily ran nightly, and rested daily, running approximately 10 hours/day for an approximate calculated total distance of 100 km over the 2-week period. Mice of both genotypes initially ran at 20–40 revolutions/minute, and increased their running performance over the subsequent 9 days to a plateau of approximately 60–80 revolutions/minute. Overall, the Myo-PGC-1αKO mice revealed a mild, non-statistically significant, reduction in exercise performance, as assessed by both the average revolutions per min (Figure 1B) and total distance run (Figure 1C). Therefore the Myo-PGC-1αKO mice provide a good system for assessing the effects of deleting PGC-1α in skeletal muscle without any of the negative effects of germline deletion of PGC-1α.

Bottom Line: The transcriptional coactivator PGC-1α, a potent regulator of metabolism in numerous tissues, is widely believed to be required for EIMB.We show here that this is not the case.Induction of metabolic genes after 2 weeks of in-cage voluntary wheel running was intact.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
Exercise confers numerous health benefits, many of which are thought to stem from exercise-induced mitochondrial biogenesis (EIMB) in skeletal muscle. The transcriptional coactivator PGC-1α, a potent regulator of metabolism in numerous tissues, is widely believed to be required for EIMB. We show here that this is not the case. Mice engineered to lack PGC-1α specifically in skeletal muscle (Myo-PGC-1αKO mice) retained intact EIMB. The exercise capacity of these mice was comparable to littermate controls. Induction of metabolic genes after 2 weeks of in-cage voluntary wheel running was intact. Electron microscopy revealed no gross abnormalities in mitochondria, and the mitochondrial biogenic response to endurance exercise was as robust in Myo-PGC-1αKO mice as in wildtype mice. The induction of enzymatic activity of the electron transport chain by exercise was likewise unperturbed in Myo-PGC-1αKO mice. These data demonstrate that PGC-1α is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle, in sharp contrast to the prevalent assumption in the field.

Show MeSH
Related in: MedlinePlus