Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, PC23
Exercise-induced stress differentially alters expression of nuclear receptor genes in mouse skeletal muscle and heart.
A. Rousseau1, J. Murdaca1, V. L. Billat2, P. A. Grimaldi1, L. Mille-Hamard2
1. INSERM U907, Université de Nice Sophia-Antipolis, Nice, France. 2. INSERM U902, Université d'Evry Val d'Essonne, Evry, France.
The transcriptional peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) is described as the master regulator of skeletal and cardiac muscle metabolism, mediating the beneficial effects of exercise (1). Its expression increases with oxidative stressors. PGC1α has been shown to regulate muscle peroxisome proliferator-activated receptor beta (PPARβ) and estrogen related-receptor alpha (ERRα) expressions. We have previously described an increase in muscle PPARβ expression with exercise training (2). It is still unclear if PGC1α has a redundant or a counteractive role with PPARβ and ERRα in response to metabolic challenges. We investigated these genes expression in both skeletal and cardiac muscles after exhaustive aerobic exercises. Heat shock protein 70/72 (HSP70/72) expression is used as a biomarker of the cellular response to stress induced by exercise loads. Two groups of FVB mice performed an exhaustive run on a treadmill at critical (CS; n=10; speed: 23.7 ± 3.4 m.min-1; duration: 55 ± 28 min) or peak speed (PS; n=10; speed: 32.3 ± 4.5 m.min-1; duration: 37 ± 30 min), whereas one group of mice remained at rest (Control; n=10). Mouse performances were individually determined by pre-test evaluations (3). Mice were sacrificed 2 hours after the end of exercise. One-way ANOVA test was used for statistical analysis. Exercise induced a significant 12 fold increase in muscle HSP70/72 expression after exercising at CS, whereas the increase after exercising at PS was not as strong. We reported here that in contrast to PGC1α, which was up-regulated, PPARβ and ERRα expressions were down-regulated in skeletal muscle in response to exercise. Our findings provided evidence to support the notion that PGC1α on one hand, and PPARβ and ERRα on the other hand, have distinct roles in the regulation of muscle adaptation to exercise, which may depend on the magnitude of the exercise-induced stress. In cardiac muscle, the increase in HSP70/72 expression was not significant and PPARβ and ERRα expressions remained unchanged. However, PGC1α was increased and the magnitude was significantly higher after CS than after PS suggesting that cardiac response to exercise is subtle and different from skeletal muscle. It is questionable if the decrease in PPARβ expression shown with these forced exercises is beneficial or harmful as such a down-regulation is not observed after voluntary exercise. Whether these responses are necessary to induce subsequent adaptations observed with chronic exercise remains to be elucidated. In heart, the preservation of PPARβ and ERRα expression may be a protection. Our results showed that exercise loads (intensity and duration) should be considered while recommending exercises for prevention or treatment of metabolic diseases.
Where applicable, experiments conform with Society ethical requirements