The drastic increase in the obesity prevalence over the last decades, and the concomitant growth in the incidence of related complications such as cardiovascular diseases, type 2 diabetes mellitus and cancer, calls for alternative treatment is an important issue, highlighting the need for alternative approaches.

Adipose tissue (AT) dysfunction is one of the hallmarks in the development of obesity-related insulin resistance. Interestingly, oxygen levels in tissues may play a key role in metabolic homeostasis in organs such as the AT, skeletal muscle (SM), liver and gut. Conflicting findings have been reported at AT pO₂ in obesity. We have recently demonstrated that AT pO₂ was higher in people with obesity, and was inversely associated with insulin sensitivity. The aim of this thesis was toinvestigate the effects of normobaric mild intermittent hypoxia (MIH) exposure on the metabolic phenotype of AT, SM, liver and the gut in overweight and obese men. Furthermore, we aimed to gain mechanistic insight in the putative metabolic and inflammatory effects of hypoxia using primary human adipocytes and myotubes. Finally, we examined the effects of hypoxic exercise on glucose homeostasis in overweight and obese men with impaired glucose homeostasis.