| First Author | Mason SD | Year | 2007 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 293 |
| Issue | 5 | Pages | R2059-69 |
| PubMed ID | 17855495 | Mgi Jnum | J:145111 |
| Mgi Id | MGI:3833516 | Doi | 10.1152/ajpregu.00335.2007 |
| Citation | Mason SD, et al. (2007) HIF-1alpha in endurance training: suppression of oxidative metabolism. Am J Physiol Regul Integr Comp Physiol 293(5):R2059-69 |
| abstractText | During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1alpha (HIF-1alpha), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1alpha in endurance training, we have created mice specifically lacking skeletal muscle HIF-1alpha and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1alpha null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1alpha null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1alpha null muscles. Additionally, HIF-1alpha null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1alpha target that inhibits oxidative metabolism. These data demonstrate that removal of HIF-1alpha causes an adaptive response in skeletal muscle akin to endurance training and provides evidence for the suppression of mitochondrial biogenesis by HIF-1alpha in normal tissue. |
