Li, Jia (2023) Skeletal muscle mitochondrial and inflammatory signaling in response to a single session of high-intensity interval exercise in hypoxia. PhD thesis, Victoria University.

Abstract

Both high-intensity interval exercise (HIIE) and hypoxia have been associated with mitochondrial biogenesis. However, limited literature has explored the effects of a single session of HIIE in hypoxia on physiological and molecular adaptive responses in human skeletal muscle and blood samples. In the current study, I combined HIIE with simulated hypoxia (3200m, oxygen fraction of 0.14) to investigate those aspects in human participants. Ten healthy male participants (Age, 28 ± 5; BMI, 26.0 ± 3.4) were recruited and completed three HIIE sessions in a random order, including one HIIE session in hypoxia (88.4% of peak oxygen uptake (VO2peak) in hypoxia, HY), one HIIE session in normoxia matched for the relative intensity of hypoxia (88.7% of VO2peak in normoxia, NR), and one HIIE session in normoxia matched for the absolute intensity of hypoxia (74.1% of VO2peak in normoxia, NA). Results from graded exercise tests suggested that hypoxia led to a decrease in VO2peak (by 20.2 ± 9.1%, p<0.01), peak power output (PPO, by 9.4 ± 2.1%, p<0.01), and lactate threshold (LT, by 13.1 ± 3.0%, p<0.01). Skeletal muscle samples were collected before (B), immediately post (P0H), 3 hours post (P3H), and 24 hours post (P24H) exercise. Mitochondrial respiration and citrate synthase activity did not differ significantly among B, P3H and P24H in the any of conditions. HIF-1α and VEGF mRNA increased at P3H in HY and NR. The downstream targets genes, including mitochondrial biogenesis-related genes (PGC-1α, PGC-1α1, PGC-1α4, PPARα), mitochondrial respiration regulators (HSP70, P53), glycolytic enzyme (PDK4, SLC27A4) and fatty-acid related genes (UCP3, CD36) increased at various time points in HY and NR (p < 0.05), but not in NA. Gene expression did not differ between HY and NR. PGC-1α protein content increased immediately after the NR session. Besides, RNA-seq was used to identify broad patterns in inflammatory gene expression in skeletal muscle and RT- PCR was then used to verify the expression of some inflammatory markers of human body. To summarise, a single session of HIIE in hypoxia is not enough to change mitochondrial respiratory function or content, but it can induce the expression of mitochondrial biogenesis-related genes, which was comparable to HIIE in normoxia matched for the relative intensity of hypoxia. However, those genes were not induced by the HIIE in normoxia matched for the absolute intensity of hypoxia. A single session of HIIE is not enough to induce changes in protein abundance, except for PGC-1α, p-AMPK and p-MTOR. Results from this study may help a better understanding of the molecular pathway as well as refine exericse protocols of HIIE in hypoxia to achieve a better outcome.

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