Comparison Of Exercise-induced Regulation Of Skeletal Muscle Hif-1α Between Endurance Trained And Untrained Individuals

Abstract

The regulation of gene transcription is essential for muscle adaptations resulting from endurance exercise training. Recent findings implicate hypoxia inducible factor 1α (HIF-1α) in this adaptive process as it regulates genes involved in O2 homeostasis and substrate utilization. Athletes have greater resting levels of muscle HIF-1α inhibitors than untrained individuals, suggesting that suppression of HIF-1α underlies skeletal muscle adaptations to endurance training. However, it is unknown if the exercise-induced expression of HIF-1α and its inhibitors differs between trained and untrained individuals. Further, differences in expression of HIF-1α target genes following acute exercise between trained (ET) and untrained (UT) individuals have yet to be examined. PURPOSE: To compare regulation of HIF-1α and HIF-1α-target genes between ET and UT individuals following acute exercise. METHODS: Five ET and five UT subjects performed an acute bout of cycling consisting of twenty, 10s sprints. Muscle samples were collected pre, post and 3 hours (3H) after exercise and analyzed for HIF-1α, the HIF-1α regulators: PHD2, FIH, VHL and SIRT6, and HIF-1α target genes (BNIP3, PINK1, VEGF, PDK-M, GLUT4, GAPDH). RESULTS: 2x3 repeated measures ANOVA revealed that post-exercise HIF-1α protein was greater in UT compared to ET individuals (.310 ± .020 vs .244 ± .001 AU, p<.05). PHD2 (.056 ± .012 vs .032 ± .023 AU), FIH (.008 ± .001 vs .004 ± .002 AU) and SIRT6 (.04 ± .001 vs .002 ± .001 AU) levels were higher in ET compared to the UT individuals at 3H post exercise (p< .05). Post-exercise fold change values for PDK (2.2 ± .1.2 vs .90 ± .21) and BNIP3 (2.2 ± 1 vs .94 ± .16) were greater in UT compared to ET (p< .05). CONCLUSION: Exercise-induced expression of HIF-1α is blunted in ET individuals compared to UT individuals. This is due to the greater post-exercise expression of HIF-1α regulating proteins. The suppression of HIF-1α in response to exercise in ET individuals is evident at the transcriptional level, as expression of PDK and BNIP3 are lower in ET individuals compared to UT. This suggests that endurance training suppresses transcription of PDK, facilitating ATP-resynthesis via oxidative phosphorylation. The suppression of BNIP3 may reflect a reduction in mitophagy, further supporting mitochondrial function in ET individuals.