In the present randomized, controlled, single-blind crossover study, we demonstrated for the first time that MIH exposure for 7 consecutive days reduces systemic oxygen saturation, decreases AT and SM pO2, evokes a shift toward glycolytic metabolism, and induces adaptations in AT and SM but does not impact AT, hepatic, or SM insulin sensitivity in men with obesity. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.