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Objective Recent studies suggest that hypoxia exposure may improve glucose homeostasis, but well-controlled human studies are lacking. We hypothesized that mild intermittent hypoxia (MIH) exposure decreases tissue oxygen partial pressure (pO2) and induces metabolic improvements in people who are overweight/obese. Methods In a randomized, controlled, single-blind crossover study, 12 men who were overweight/obese were exposed to MIH (15 % O2, 3 × 2 h/day) or normoxia (21 % O2) for 7 consecutive days. Adipose tissue (AT) and skeletal muscle (SM) pO2, fasting/postprandial substrate metabolism, tissue-specific insulin sensitivity, SM oxidative capacity, and AT and SM gene/protein expression were determined. Furthermore, primary human myotubes and adipocytes were exposed to oxygen levels mimicking the hypoxic and normoxic AT and SM microenvironments. Results MIH decreased systemic oxygen saturation (92.0 ± 0.5 % vs 97.1 ± 0.3, p, Highlights • MIH exposure decreases oxygen partial pressure in human adipose tissue and skeletal muscle. • MIH exposure induces a shift in substrate utilization toward glycolytic metabolism. • Hypoxia exposure increases insulin-independent glucose uptake in primary human myotubes, at least in part through AMPK. • MIH does not alter adipose tissue, hepatic and peripheral insulin sensitivity.

Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low‐grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results. Here, we will review the role of adipose tissue oxygenation in the pathophysiology of obesity‐related complications, with a specific focus on human studies. We will provide an overview of the determinants of adipose tissue oxygenation, as well as the role of adipose tissue oxygenation in glucose homeostasis, lipid metabolism and inflammation. Finally, we will discuss the putative effects of physiological and experimental hypoxia on adipose tissue biology and whole‐body metabolism in humans. We conclude that several lines of evidence suggest that alteration of adipose tissue oxygenation may impact metabolic homeostasis, thereby providing a novel strategy to combat chronic metabolic diseases in obese humans.

Adipose tissue is a highly dynamic, metabolically active organ involved in a multitude of physiological processes. The expansion of adipose tissue during the development of obesity is often accompanied by adipose tissue dysfunction, which in turn contributes to metabolic and endocrine derangements. Indeed, adipose tissue dysfunction, which is characterized by adipocyte hypertrophy, impaired lipid metabolism, inflammation, a disproportionate deposition of extracellular matrix components, and inadequate vascularization, seems to play a prominent role in insulin resistance and systemic low-grade inflammation. In this chapter, the metabolic and immunological consequences of adipose tissue dysfunction in obesity are discussed. Moreover, we will elaborate on the possible link between adipose tissue dysfunction and lung diseases. Targeting adipose tissue dysfunction may provide a valuable strategy to improve cardiometabolic health and pulmonary function in obese individuals and individuals with sarcopenia, who are characterized by a relative excess of adipose tissue.