Mild intermittent hypoxia exposure induces metabolic and molecular adaptations in men with obesity

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.