Obesity is now a worldwide epidemic which has driven a compelling demand for innovative weight loss programmes. Pioneering investigations have reported that oxygen (O2) variations in humans may produce changes in body composition. In support, reductions in body mass are consistently reported in lowlanders staying at high-altitude. Therefore, it is hypothesised that the hypoxic stimulus associated with this environment, with or without the addition of exercise, could be used as a non-pharmacological therapy for obesity. Using both in vitro and in vivo techniques, in this thesis, this method for weight loss is explored.

Using physiological hypoxia (5% O2), study 1 demonstrated that 24 hours of normobaric hypoxic exposure did not significantly affect myoblast proliferation as determined by cell counts and cell viability. In addition, mRNA expression levels of genes associated with myoblast cell proliferation (myoD, myogenin and myf5) remained unchanged. Study 2 demonstrated that myotubes exposed to 24 hours of hypoxia (5% O2) significantly increased the mRNA expression of MURF-1, MAFbx, and myostatin compared to the normoxic control exposure (21% O2). IGF-1 mRNA was significantly reduced following 24 hours of hypoxia. However, when the length of exposure was reduced to 90 minutes, a significant increase in MURF-1 and MAFbx, but no change was observed for IGF-1 mRNA expression. These results demonstrate that while acute normobaric hypoxia appears to have no detrimental effect on myoblasts, the effect of hypoxia on myotubes can be detrimental as demonstrated by an increased expression of skeletal muscle atrophy genes; however the volume of this response appears to be exposure dependent. Therefore, when conducting human studies, length of hypoxic exposure should be a primary concern.

Study 3 demonstrated that body mass and body composition are unchanged following a 4-week intermittent hypoxic exposure programme compared with a normoxic control period. Blood pressure, resting metabolic rate, respiratory exchange ratio, fasting blood glucose, blood lipid profile parameters and aerobic capacity, also remained unchanged. Leptin and adiponectin, two key appetite hormones were not significantly altered with intermittent hypoxic exposure.

The results of study 4 suggest that the use of age-predicted equations for the prescription of exercise intensity in hypoxia are inadequate. There was no significant reduction in peak heart rate in hypoxia (1000, 2000, 3000, 4000 m) when compared with normoxia, however, all 11 age-predicted equations over-estimated peak heart rate in at least 3 conditions or more. On the contrary, study 4 demonstrated that the ventilatory threshold is not reduced in hypoxia when compared to normoxia, which suggests it is a good model for the prescription of exercise intensity in normobaric hypoxia.

The conclusions drawn from this thesis are; (1) cell proliferation is maintained under hypoxic (5% O2) conditions, (2) myotubes exposed to 90 minutes or 24 hours of hypoxia (5% O2) show increased protein degradation, as demonstrated by an increase in skeletal muscle atrophy genes MURF-1 and MAFbx, which following 24 hours can be explained by an increase in myostatin and decrease in IGF-1 however the same principle does not appear to explain the response at 90 minutes, (4) intermittent hypoxic exposures do not result in significant weight loss, or improve risk markers associated with excess body mass, which may suggest that exercise is a key component in intermittent hypoxic training programmes not hypoxic exposure per se, (5) leptin and adiponectin are not altered with IHE, and finally, (6) peak heart rate is not an accurate measure for exercise intensity prescription in hypoxia, but use of ventilatory threshold is promising.

Overall, the use of hypoxia as a non-pharmacological therapy for obesity still warrants further exploration. It has been demonstrated in this thesis that 4 weeks of intermittent hypoxic exposures (90 min·d-1, 3d·wk-1) does not reduce body mass or other associated metabolic health risks. Therefore, it appears that intermittent hypoxic exposures alone without the combination of exercise is not sufficient enough to induce weight loss suggesting that exercise and hypoxia should be combined within weight loss interventions designed to produce significant losses in body mass. In the design of an intermittent hypoxic training programme, the ventilatory threshold has been shown to be an appropriate method to determine exercise intensity in normobaric hypoxia, however equations used to predict peak heart rate should be avoided.