| First Author | Pérez-Schindler J | Year | 2014 |
| Journal | Diabetologia | Volume | 57 |
| Issue | 11 | Pages | 2405-12 |
| PubMed ID | 25116175 | Mgi Jnum | J:218721 |
| Mgi Id | MGI:5618231 | Doi | 10.1007/s00125-014-3352-3 |
| Citation | Perez-Schindler J, et al. (2014) The coactivator PGC-1alpha regulates skeletal muscle oxidative metabolism independently of the nuclear receptor PPARbeta/delta in sedentary mice fed a regular chow diet. Diabetologia 57(11):2405-12 |
| abstractText | AIMS/HYPOTHESIS: Physical activity improves oxidative capacity and exerts therapeutic beneficial effects, particularly in the context of metabolic diseases. The peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1alpha (PGC-1alpha) and the nuclear receptor PPARbeta/delta have both been independently discovered to play a pivotal role in the regulation of oxidative metabolism in skeletal muscle, though their interdependence remains unclear. Hence, our aim was to determine the functional interaction between these two factors in mouse skeletal muscle in vivo. METHODS: Adult male control mice, PGC-1alpha muscle-specific transgenic (mTg) mice, PPARbeta/delta muscle-specific knockout (mKO) mice and the combination PPARbeta/delta mKO + PGC-1alpha mTg mice were studied under basal conditions and following PPARbeta/delta agonist administration and acute exercise. Whole-body metabolism was assessed by indirect calorimetry and blood analysis, while magnetic resonance was used to measure body composition. Quantitative PCR and western blot were used to determine gene expression and intracellular signalling. The proportion of oxidative muscle fibre was determined by NADH staining. RESULTS: Agonist-induced PPARbeta/delta activation was only disrupted by PPARbeta/delta knockout. We also found that the disruption of the PGC-1alpha-PPARbeta/delta axis did not affect whole-body metabolism under basal conditions. As expected, PGC-1alpha mTg mice exhibited higher exercise performance, peak oxygen consumption and lower blood lactate levels following exercise, though PPARbeta/delta mKO + PGC-1alpha mTg mice showed a similar phenotype. Similarly, we found that PPARbeta/delta was dispensable for PGC-1alpha-mediated enhancement of an oxidative phenotype in skeletal muscle. CONCLUSIONS/INTERPRETATION: Collectively, these results indicate that PPARbeta/delta is not an essential partner of PGC-1alpha in the control of skeletal muscle energy metabolism. |
