| First Author | Botta A | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 8 | Pages | e70248 |
| PubMed ID | 23936397 | Mgi Jnum | J:205777 |
| Mgi Id | MGI:5546444 | Doi | 10.1371/journal.pone.0070248 |
| Citation | Botta A, et al. (2013) Short term exercise induces PGC-1alpha, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts. PLoS One 8(8):e70248 |
| abstractText | PGC-1alpha, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1alpha is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1alpha on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1alpha without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFalpha) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1alpha such as NRF-1 and several respiratory genes. Such mismatch between PGC-1alpha and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1alpha expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1alpha mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age. |
